AICAR Enhances the Phagocytic Ability of Macrophages towards Apoptotic Cells through P38 Mitogen Activated Protein Kinase Activation Independent of AMP-Activated Protein Kinase
Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by ma...
Gespeichert in:
| Veröffentlicht in: | PloS one 2015-05, Vol.10 (5), p.e0127885-e0127885 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0127885 |
|---|---|
| container_issue | 5 |
| container_start_page | e0127885 |
| container_title | PloS one |
| container_volume | 10 |
| creator | Quan, Hui Kim, Joung-Min Lee, Hyun-Jung Lee, Seong-Heon Choi, Jeong-Il Bae, Hong-Beom |
| description | Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by macrophages, known as efferocytosis, which is essential in maintaining tissue homeostasis and resolving inflammation. AICAR increased p38 MAPK activation and the phagocytosis of apoptotic cells by macrophages, which were inhibited by the p38 MAPK inhibitor, SB203580, the TGF-beta-activated kinase 1 (TAK1) inhibitor, (5Z)-7-oxozeaenol, and siRNA-mediated knock-down of p38α. AICAR increased phosphorylation of Akt, but the inhibition of PI3K/Akt activity using LY294002 did not affect the AICAR-induced changes in efferocytosis in macrophages. CGS15943, a non-selective adenosine receptor antagonist, did not affect AICAR-induced changes in efferocytosis, but dipyridamole, an adenosine transporter inhibitor, diminished the AICAR-mediated increases in efferocytosis. AICAR-induced p38 MAPK phosphorylation was not inhibited by the AMPK inhibitor, compound C, or siRNA-mediated knock-down of AMPKα1. Inhibition of AMPK using compound C or 5'-iodotubercidin did not completely block AICAR-mediated increases in efferocytosis. Furthermore, AICAR also increased the removal of apoptotic neutrophils or thymocytes in mouse lungs. These results reveal a novel mechanism by which AICAR increases macrophage-mediated phagocytosis of apoptotic cells and suggest that AICAR may be used to treat efferocytosis-related inflammatory conditions. |
| doi_str_mv | 10.1371/journal.pone.0127885 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1683763146</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A432553100</galeid><doaj_id>oai_doaj_org_article_2881579537bd415ea6a147715206bca2</doaj_id><sourcerecordid>A432553100</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-b614d27d5f68d9da715ea437249f064c313ca9aaa038d371a9cb15b245ec8ea03</originalsourceid><addsrcrecordid>eNqNk21r1TAUx4sobk6_gWhAEH1xr81Tm74Ryph6cWOX-fA2nKZpm9Gb1Cad7lv5EU23u7ErE6TQlnN-5-mfnCR5jtMlpjl-d-6m0UK_HJzVyxSTXAj-INnHBSWLjKT04Z3_veSJ9-dpyqnIssfJHslSkhY52U9-l6vD8gwd2Q6s0h6FTqN1B61Tl8EoVFamN-ESuQadgBrdEF0z5X7CWHtUDm4IbgYPdd_P0aOb2g6tqUAnJrhWW1SqYC4g6BqtRxe0seizseD1jcM4i1a21oOOLxvmUuXJevGvsKfJowZ6r59tvwfJtw9HXw8_LY5PP8ZRjhcq5yIsqgyzmuQ1bzJRFzXkmGtgNCesaNKMKYqpggIAUirqKCcUqsK8IoxrJXS0HiQvr_MOvfNyK7aXOBM0zyhmWSRW10Tt4FwOo9nAeCkdGHllcGMrYYza9FoSITDPC07zqmZzJxlglseeSJpVCkjM9X5bbao2ulZRiBH6naS7Hms62boLyRjLGZ-bebNNMLofk_ZBboxX8VDAajdd9c0Y5UKIiL76C71_ui3VQhzA2MbFumpOKktGCecUp7NKy3uo-NR6Y1S8mY2J9p2AtzsBkQn6V2hh8l6uvpz9P3v6fZd9fYftNPSh866f5uvld0F2Dcbb7P2om1uRcSrnxbpRQ86LJbeLFcNe3D2g26CbTaJ_AEjNHj0</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1683763146</pqid></control><display><type>article</type><title>AICAR Enhances the Phagocytic Ability of Macrophages towards Apoptotic Cells through P38 Mitogen Activated Protein Kinase Activation Independent of AMP-Activated Protein Kinase</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Quan, Hui ; Kim, Joung-Min ; Lee, Hyun-Jung ; Lee, Seong-Heon ; Choi, Jeong-Il ; Bae, Hong-Beom</creator><creatorcontrib>Quan, Hui ; Kim, Joung-Min ; Lee, Hyun-Jung ; Lee, Seong-Heon ; Choi, Jeong-Il ; Bae, Hong-Beom</creatorcontrib><description>Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by macrophages, known as efferocytosis, which is essential in maintaining tissue homeostasis and resolving inflammation. AICAR increased p38 MAPK activation and the phagocytosis of apoptotic cells by macrophages, which were inhibited by the p38 MAPK inhibitor, SB203580, the TGF-beta-activated kinase 1 (TAK1) inhibitor, (5Z)-7-oxozeaenol, and siRNA-mediated knock-down of p38α. AICAR increased phosphorylation of Akt, but the inhibition of PI3K/Akt activity using LY294002 did not affect the AICAR-induced changes in efferocytosis in macrophages. CGS15943, a non-selective adenosine receptor antagonist, did not affect AICAR-induced changes in efferocytosis, but dipyridamole, an adenosine transporter inhibitor, diminished the AICAR-mediated increases in efferocytosis. AICAR-induced p38 MAPK phosphorylation was not inhibited by the AMPK inhibitor, compound C, or siRNA-mediated knock-down of AMPKα1. Inhibition of AMPK using compound C or 5'-iodotubercidin did not completely block AICAR-mediated increases in efferocytosis. Furthermore, AICAR also increased the removal of apoptotic neutrophils or thymocytes in mouse lungs. These results reveal a novel mechanism by which AICAR increases macrophage-mediated phagocytosis of apoptotic cells and suggest that AICAR may be used to treat efferocytosis-related inflammatory conditions.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0127885</identifier><identifier>PMID: 26020972</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adenosine ; Adenosine kinase ; Adenosine monophosphate ; AKT protein ; Aminoimidazole Carboxamide - analogs & derivatives ; Aminoimidazole Carboxamide - pharmacology ; AMP ; AMP-activated protein kinase ; AMP-Activated Protein Kinases - antagonists & inhibitors ; AMP-Activated Protein Kinases - genetics ; AMP-Activated Protein Kinases - metabolism ; Anesthesiology ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - genetics ; Bone morphogenetic proteins ; Cell activation ; Cell cycle ; Dipyridamole ; Enzyme Activation - drug effects ; Enzyme Activation - genetics ; Enzyme inhibitors ; Gene Knockdown Techniques ; Growth factors ; Homeostasis ; Imidazoles - pharmacology ; Inflammation ; Inhibition ; Inhibitors ; Kinases ; Laboratory animals ; Leukocytes (neutrophilic) ; Lungs ; Macrophages ; Macrophages, Peritoneal - enzymology ; Male ; MAP kinase ; MAP Kinase Kinase Kinases - antagonists & inhibitors ; MAP Kinase Kinase Kinases - genetics ; MAP Kinase Kinase Kinases - metabolism ; Medical schools ; Medicine ; Mice ; Mice, Inbred BALB C ; Mitogens ; Neutrophils ; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases - genetics ; p38 Mitogen-Activated Protein Kinases - metabolism ; Pain ; Penicillin ; Phagocytes ; Phagocytosis ; Phagocytosis - drug effects ; Phagocytosis - genetics ; Phosphorylation ; Phosphorylation - drug effects ; Phosphorylation - genetics ; Protein kinases ; Proteins ; Pyridines - pharmacology ; Ribonucleotides - pharmacology ; siRNA ; Stem cells ; Studies ; TAK1 protein ; Thymocytes ; Transforming growth factor-b ; Transforming growth factors ; Transporter</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0127885-e0127885</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Quan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Quan et al 2015 Quan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-b614d27d5f68d9da715ea437249f064c313ca9aaa038d371a9cb15b245ec8ea03</citedby><cites>FETCH-LOGICAL-c758t-b614d27d5f68d9da715ea437249f064c313ca9aaa038d371a9cb15b245ec8ea03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447456/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447456/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26020972$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quan, Hui</creatorcontrib><creatorcontrib>Kim, Joung-Min</creatorcontrib><creatorcontrib>Lee, Hyun-Jung</creatorcontrib><creatorcontrib>Lee, Seong-Heon</creatorcontrib><creatorcontrib>Choi, Jeong-Il</creatorcontrib><creatorcontrib>Bae, Hong-Beom</creatorcontrib><title>AICAR Enhances the Phagocytic Ability of Macrophages towards Apoptotic Cells through P38 Mitogen Activated Protein Kinase Activation Independent of AMP-Activated Protein Kinase</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by macrophages, known as efferocytosis, which is essential in maintaining tissue homeostasis and resolving inflammation. AICAR increased p38 MAPK activation and the phagocytosis of apoptotic cells by macrophages, which were inhibited by the p38 MAPK inhibitor, SB203580, the TGF-beta-activated kinase 1 (TAK1) inhibitor, (5Z)-7-oxozeaenol, and siRNA-mediated knock-down of p38α. AICAR increased phosphorylation of Akt, but the inhibition of PI3K/Akt activity using LY294002 did not affect the AICAR-induced changes in efferocytosis in macrophages. CGS15943, a non-selective adenosine receptor antagonist, did not affect AICAR-induced changes in efferocytosis, but dipyridamole, an adenosine transporter inhibitor, diminished the AICAR-mediated increases in efferocytosis. AICAR-induced p38 MAPK phosphorylation was not inhibited by the AMPK inhibitor, compound C, or siRNA-mediated knock-down of AMPKα1. Inhibition of AMPK using compound C or 5'-iodotubercidin did not completely block AICAR-mediated increases in efferocytosis. Furthermore, AICAR also increased the removal of apoptotic neutrophils or thymocytes in mouse lungs. These results reveal a novel mechanism by which AICAR increases macrophage-mediated phagocytosis of apoptotic cells and suggest that AICAR may be used to treat efferocytosis-related inflammatory conditions.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adenosine</subject><subject>Adenosine kinase</subject><subject>Adenosine monophosphate</subject><subject>AKT protein</subject><subject>Aminoimidazole Carboxamide - analogs & derivatives</subject><subject>Aminoimidazole Carboxamide - pharmacology</subject><subject>AMP</subject><subject>AMP-activated protein kinase</subject><subject>AMP-Activated Protein Kinases - antagonists & inhibitors</subject><subject>AMP-Activated Protein Kinases - genetics</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Anesthesiology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Bone morphogenetic proteins</subject><subject>Cell activation</subject><subject>Cell cycle</subject><subject>Dipyridamole</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Activation - genetics</subject><subject>Enzyme inhibitors</subject><subject>Gene Knockdown Techniques</subject><subject>Growth factors</subject><subject>Homeostasis</subject><subject>Imidazoles - pharmacology</subject><subject>Inflammation</subject><subject>Inhibition</subject><subject>Inhibitors</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lungs</subject><subject>Macrophages</subject><subject>Macrophages, Peritoneal - enzymology</subject><subject>Male</subject><subject>MAP kinase</subject><subject>MAP Kinase Kinase Kinases - antagonists & inhibitors</subject><subject>MAP Kinase Kinase Kinases - genetics</subject><subject>MAP Kinase Kinase Kinases - metabolism</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mitogens</subject><subject>Neutrophils</subject><subject>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>p38 Mitogen-Activated Protein Kinases - genetics</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Pain</subject><subject>Penicillin</subject><subject>Phagocytes</subject><subject>Phagocytosis</subject><subject>Phagocytosis - drug effects</subject><subject>Phagocytosis - genetics</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Phosphorylation - genetics</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Pyridines - pharmacology</subject><subject>Ribonucleotides - pharmacology</subject><subject>siRNA</subject><subject>Stem cells</subject><subject>Studies</subject><subject>TAK1 protein</subject><subject>Thymocytes</subject><subject>Transforming growth factor-b</subject><subject>Transforming growth factors</subject><subject>Transporter</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk21r1TAUx4sobk6_gWhAEH1xr81Tm74Ryph6cWOX-fA2nKZpm9Gb1Cad7lv5EU23u7ErE6TQlnN-5-mfnCR5jtMlpjl-d-6m0UK_HJzVyxSTXAj-INnHBSWLjKT04Z3_veSJ9-dpyqnIssfJHslSkhY52U9-l6vD8gwd2Q6s0h6FTqN1B61Tl8EoVFamN-ESuQadgBrdEF0z5X7CWHtUDm4IbgYPdd_P0aOb2g6tqUAnJrhWW1SqYC4g6BqtRxe0seizseD1jcM4i1a21oOOLxvmUuXJevGvsKfJowZ6r59tvwfJtw9HXw8_LY5PP8ZRjhcq5yIsqgyzmuQ1bzJRFzXkmGtgNCesaNKMKYqpggIAUirqKCcUqsK8IoxrJXS0HiQvr_MOvfNyK7aXOBM0zyhmWSRW10Tt4FwOo9nAeCkdGHllcGMrYYza9FoSITDPC07zqmZzJxlglseeSJpVCkjM9X5bbao2ulZRiBH6naS7Hms62boLyRjLGZ-bebNNMLofk_ZBboxX8VDAajdd9c0Y5UKIiL76C71_ui3VQhzA2MbFumpOKktGCecUp7NKy3uo-NR6Y1S8mY2J9p2AtzsBkQn6V2hh8l6uvpz9P3v6fZd9fYftNPSh866f5uvld0F2Dcbb7P2om1uRcSrnxbpRQ86LJbeLFcNe3D2g26CbTaJ_AEjNHj0</recordid><startdate>20150528</startdate><enddate>20150528</enddate><creator>Quan, Hui</creator><creator>Kim, Joung-Min</creator><creator>Lee, Hyun-Jung</creator><creator>Lee, Seong-Heon</creator><creator>Choi, Jeong-Il</creator><creator>Bae, Hong-Beom</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150528</creationdate><title>AICAR Enhances the Phagocytic Ability of Macrophages towards Apoptotic Cells through P38 Mitogen Activated Protein Kinase Activation Independent of AMP-Activated Protein Kinase</title><author>Quan, Hui ; Kim, Joung-Min ; Lee, Hyun-Jung ; Lee, Seong-Heon ; Choi, Jeong-Il ; Bae, Hong-Beom</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-b614d27d5f68d9da715ea437249f064c313ca9aaa038d371a9cb15b245ec8ea03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adenosine</topic><topic>Adenosine kinase</topic><topic>Adenosine monophosphate</topic><topic>AKT protein</topic><topic>Aminoimidazole Carboxamide - analogs & derivatives</topic><topic>Aminoimidazole Carboxamide - pharmacology</topic><topic>AMP</topic><topic>AMP-activated protein kinase</topic><topic>AMP-Activated Protein Kinases - antagonists & inhibitors</topic><topic>AMP-Activated Protein Kinases - genetics</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Anesthesiology</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>Bone morphogenetic proteins</topic><topic>Cell activation</topic><topic>Cell cycle</topic><topic>Dipyridamole</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Activation - genetics</topic><topic>Enzyme inhibitors</topic><topic>Gene Knockdown Techniques</topic><topic>Growth factors</topic><topic>Homeostasis</topic><topic>Imidazoles - pharmacology</topic><topic>Inflammation</topic><topic>Inhibition</topic><topic>Inhibitors</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lungs</topic><topic>Macrophages</topic><topic>Macrophages, Peritoneal - enzymology</topic><topic>Male</topic><topic>MAP kinase</topic><topic>MAP Kinase Kinase Kinases - antagonists & inhibitors</topic><topic>MAP Kinase Kinase Kinases - genetics</topic><topic>MAP Kinase Kinase Kinases - metabolism</topic><topic>Medical schools</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mitogens</topic><topic>Neutrophils</topic><topic>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>p38 Mitogen-Activated Protein Kinases - genetics</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Pain</topic><topic>Penicillin</topic><topic>Phagocytes</topic><topic>Phagocytosis</topic><topic>Phagocytosis - drug effects</topic><topic>Phagocytosis - genetics</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Phosphorylation - genetics</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Pyridines - pharmacology</topic><topic>Ribonucleotides - pharmacology</topic><topic>siRNA</topic><topic>Stem cells</topic><topic>Studies</topic><topic>TAK1 protein</topic><topic>Thymocytes</topic><topic>Transforming growth factor-b</topic><topic>Transforming growth factors</topic><topic>Transporter</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quan, Hui</creatorcontrib><creatorcontrib>Kim, Joung-Min</creatorcontrib><creatorcontrib>Lee, Hyun-Jung</creatorcontrib><creatorcontrib>Lee, Seong-Heon</creatorcontrib><creatorcontrib>Choi, Jeong-Il</creatorcontrib><creatorcontrib>Bae, Hong-Beom</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quan, Hui</au><au>Kim, Joung-Min</au><au>Lee, Hyun-Jung</au><au>Lee, Seong-Heon</au><au>Choi, Jeong-Il</au><au>Bae, Hong-Beom</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AICAR Enhances the Phagocytic Ability of Macrophages towards Apoptotic Cells through P38 Mitogen Activated Protein Kinase Activation Independent of AMP-Activated Protein Kinase</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-28</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0127885</spage><epage>e0127885</epage><pages>e0127885-e0127885</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by macrophages, known as efferocytosis, which is essential in maintaining tissue homeostasis and resolving inflammation. AICAR increased p38 MAPK activation and the phagocytosis of apoptotic cells by macrophages, which were inhibited by the p38 MAPK inhibitor, SB203580, the TGF-beta-activated kinase 1 (TAK1) inhibitor, (5Z)-7-oxozeaenol, and siRNA-mediated knock-down of p38α. AICAR increased phosphorylation of Akt, but the inhibition of PI3K/Akt activity using LY294002 did not affect the AICAR-induced changes in efferocytosis in macrophages. CGS15943, a non-selective adenosine receptor antagonist, did not affect AICAR-induced changes in efferocytosis, but dipyridamole, an adenosine transporter inhibitor, diminished the AICAR-mediated increases in efferocytosis. AICAR-induced p38 MAPK phosphorylation was not inhibited by the AMPK inhibitor, compound C, or siRNA-mediated knock-down of AMPKα1. Inhibition of AMPK using compound C or 5'-iodotubercidin did not completely block AICAR-mediated increases in efferocytosis. Furthermore, AICAR also increased the removal of apoptotic neutrophils or thymocytes in mouse lungs. These results reveal a novel mechanism by which AICAR increases macrophage-mediated phagocytosis of apoptotic cells and suggest that AICAR may be used to treat efferocytosis-related inflammatory conditions.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26020972</pmid><doi>10.1371/journal.pone.0127885</doi><tpages>e0127885</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0127885-e0127885 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1683763146 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | 1-Phosphatidylinositol 3-kinase Adenosine Adenosine kinase Adenosine monophosphate AKT protein Aminoimidazole Carboxamide - analogs & derivatives Aminoimidazole Carboxamide - pharmacology AMP AMP-activated protein kinase AMP-Activated Protein Kinases - antagonists & inhibitors AMP-Activated Protein Kinases - genetics AMP-Activated Protein Kinases - metabolism Anesthesiology Animals Apoptosis Apoptosis - drug effects Apoptosis - genetics Bone morphogenetic proteins Cell activation Cell cycle Dipyridamole Enzyme Activation - drug effects Enzyme Activation - genetics Enzyme inhibitors Gene Knockdown Techniques Growth factors Homeostasis Imidazoles - pharmacology Inflammation Inhibition Inhibitors Kinases Laboratory animals Leukocytes (neutrophilic) Lungs Macrophages Macrophages, Peritoneal - enzymology Male MAP kinase MAP Kinase Kinase Kinases - antagonists & inhibitors MAP Kinase Kinase Kinases - genetics MAP Kinase Kinase Kinases - metabolism Medical schools Medicine Mice Mice, Inbred BALB C Mitogens Neutrophils p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors p38 Mitogen-Activated Protein Kinases - genetics p38 Mitogen-Activated Protein Kinases - metabolism Pain Penicillin Phagocytes Phagocytosis Phagocytosis - drug effects Phagocytosis - genetics Phosphorylation Phosphorylation - drug effects Phosphorylation - genetics Protein kinases Proteins Pyridines - pharmacology Ribonucleotides - pharmacology siRNA Stem cells Studies TAK1 protein Thymocytes Transforming growth factor-b Transforming growth factors Transporter |
| title | AICAR Enhances the Phagocytic Ability of Macrophages towards Apoptotic Cells through P38 Mitogen Activated Protein Kinase Activation Independent of AMP-Activated Protein Kinase |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T23%3A58%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AICAR%20Enhances%20the%20Phagocytic%20Ability%20of%20Macrophages%20towards%20Apoptotic%20Cells%20through%20P38%20Mitogen%20Activated%20Protein%20Kinase%20Activation%20Independent%20of%20AMP-Activated%20Protein%20Kinase&rft.jtitle=PloS%20one&rft.au=Quan,%20Hui&rft.date=2015-05-28&rft.volume=10&rft.issue=5&rft.spage=e0127885&rft.epage=e0127885&rft.pages=e0127885-e0127885&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0127885&rft_dat=%3Cgale_plos_%3EA432553100%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1683763146&rft_id=info:pmid/26020972&rft_galeid=A432553100&rft_doaj_id=oai_doaj_org_article_2881579537bd415ea6a147715206bca2&rfr_iscdi=true |