IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression
Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2015-05, Vol.460 (2), p.320-326 |
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| creator | Kiyomiya, Hiroyasu Ariyoshi, Wataru Okinaga, Toshinori Kaneuji, Takeshi Mitsugi, Sho Sakurai, Takuma Habu, Manabu Yoshioka, Izumi Tominaga, Kazuhiro Nishihara, Tatsuji |
| description | Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression.
•IL-33 inhibits RANKL-induced osteoclast formation.•IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression.•IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8. |
| doi_str_mv | 10.1016/j.bbrc.2015.03.033 |
| format | Article |
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•IL-33 inhibits RANKL-induced osteoclast formation.•IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression.•IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2015.03.033</identifier><identifier>PMID: 25795135</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ACID PHOSPHATASE ; Animals ; Base Sequence ; Blimp-1 ; BONE MARROW CELLS ; CATHEPSINS ; Cell Line ; Cells, Cultured ; CESIUM FLUORIDES ; DNA Primers ; Female ; GENES ; IL-33 ; IN VITRO ; INHIBITION ; INTERFERON ; Interferon Regulatory Factors - genetics ; Interferon Regulatory Factors - metabolism ; Interleukin-33 ; Interleukins - physiology ; IRF-8 ; LIGANDS ; LYMPHOCYTES ; MACROPHAGES ; Male ; MICE ; MONOCYTES ; NFATC Transcription Factors - genetics ; NFATC Transcription Factors - metabolism ; Osteoclastogenesis ; Osteoclasts - cytology ; Positive Regulatory Domain I-Binding Factor 1 ; RANK Ligand - antagonists & inhibitors ; RANK Ligand - physiology ; Real-Time Polymerase Chain Reaction ; RECEPTORS ; REGULATIONS ; Signal Transduction ; STIMULATION ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Biochemical and biophysical research communications, 2015-05, Vol.460 (2), p.320-326</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-a2323b3d5dd1434d6072c7c7ab7161b9b320d17281a5446a0cdac3834273f0a3</citedby><cites>FETCH-LOGICAL-c553t-a2323b3d5dd1434d6072c7c7ab7161b9b320d17281a5446a0cdac3834273f0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X15004684$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25795135$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22462019$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Kiyomiya, Hiroyasu</creatorcontrib><creatorcontrib>Ariyoshi, Wataru</creatorcontrib><creatorcontrib>Okinaga, Toshinori</creatorcontrib><creatorcontrib>Kaneuji, Takeshi</creatorcontrib><creatorcontrib>Mitsugi, Sho</creatorcontrib><creatorcontrib>Sakurai, Takuma</creatorcontrib><creatorcontrib>Habu, Manabu</creatorcontrib><creatorcontrib>Yoshioka, Izumi</creatorcontrib><creatorcontrib>Tominaga, Kazuhiro</creatorcontrib><creatorcontrib>Nishihara, Tatsuji</creatorcontrib><title>IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression.
•IL-33 inhibits RANKL-induced osteoclast formation.•IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression.•IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ACID PHOSPHATASE</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Blimp-1</subject><subject>BONE MARROW CELLS</subject><subject>CATHEPSINS</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>CESIUM FLUORIDES</subject><subject>DNA Primers</subject><subject>Female</subject><subject>GENES</subject><subject>IL-33</subject><subject>IN VITRO</subject><subject>INHIBITION</subject><subject>INTERFERON</subject><subject>Interferon Regulatory Factors - genetics</subject><subject>Interferon Regulatory Factors - metabolism</subject><subject>Interleukin-33</subject><subject>Interleukins - physiology</subject><subject>IRF-8</subject><subject>LIGANDS</subject><subject>LYMPHOCYTES</subject><subject>MACROPHAGES</subject><subject>Male</subject><subject>MICE</subject><subject>MONOCYTES</subject><subject>NFATC Transcription Factors - genetics</subject><subject>NFATC Transcription Factors - metabolism</subject><subject>Osteoclastogenesis</subject><subject>Osteoclasts - cytology</subject><subject>Positive Regulatory Domain I-Binding Factor 1</subject><subject>RANK Ligand - antagonists & inhibitors</subject><subject>RANK Ligand - physiology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RECEPTORS</subject><subject>REGULATIONS</subject><subject>Signal Transduction</subject><subject>STIMULATION</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFrFTEQx4NY7LP6BTxIwIuXvCaZ3eQteKnF6qMPhdKDt5BNst08djfPJCv67c2y1aOFgYGZ3_yZmT9CbxjdMsrE5XHbttFsOWX1lkIJeIY2jDaUcEar52hDKRWEN-z7OXqZ0pFSxirRvEDnvJZNzaDeoH5_IADYT71vfU747urr7YH4yc7GWRxSdsEMOmXchTjq7MOEcx_D_NCX7HB0D_OwlkOHPw5-PBGG9WTx_u6G7LD7dYoupdJ_hc46PST3-jFfoPubT_fXX8jh2-f99dWBmLqGTDQHDi3Y2lpWQWUFldxII3UrmWBt0wKnlkm-Y7quKqGpsdrADiouoaMaLtC7Vbas7lUyPjvTmzBNzmTFeSXKt5pCvV-pUww_ZpeyGn0ybhj05MKcFJPAd5w3jXgaFVIANILzgvIVNTGkFF2nTtGPOv5WjKrFMXVUi2NqcUxRKAFl6O2j_tyOzv4b-WtRAT6sgCtf--ldXK5yU7HHx-UoG_z_9P8A8gWkVQ</recordid><startdate>20150501</startdate><enddate>20150501</enddate><creator>Kiyomiya, Hiroyasu</creator><creator>Ariyoshi, Wataru</creator><creator>Okinaga, Toshinori</creator><creator>Kaneuji, Takeshi</creator><creator>Mitsugi, Sho</creator><creator>Sakurai, Takuma</creator><creator>Habu, Manabu</creator><creator>Yoshioka, Izumi</creator><creator>Tominaga, Kazuhiro</creator><creator>Nishihara, Tatsuji</creator><general>Elsevier Inc</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>7X8</scope><scope>7QP</scope><scope>OTOTI</scope></search><sort><creationdate>20150501</creationdate><title>IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression</title><author>Kiyomiya, Hiroyasu ; Ariyoshi, Wataru ; Okinaga, Toshinori ; Kaneuji, Takeshi ; Mitsugi, Sho ; Sakurai, Takuma ; Habu, Manabu ; Yoshioka, Izumi ; Tominaga, Kazuhiro ; Nishihara, Tatsuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-a2323b3d5dd1434d6072c7c7ab7161b9b320d17281a5446a0cdac3834273f0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ACID PHOSPHATASE</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Blimp-1</topic><topic>BONE MARROW CELLS</topic><topic>CATHEPSINS</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>CESIUM FLUORIDES</topic><topic>DNA Primers</topic><topic>Female</topic><topic>GENES</topic><topic>IL-33</topic><topic>IN VITRO</topic><topic>INHIBITION</topic><topic>INTERFERON</topic><topic>Interferon Regulatory Factors - genetics</topic><topic>Interferon Regulatory Factors - metabolism</topic><topic>Interleukin-33</topic><topic>Interleukins - physiology</topic><topic>IRF-8</topic><topic>LIGANDS</topic><topic>LYMPHOCYTES</topic><topic>MACROPHAGES</topic><topic>Male</topic><topic>MICE</topic><topic>MONOCYTES</topic><topic>NFATC Transcription Factors - genetics</topic><topic>NFATC Transcription Factors - metabolism</topic><topic>Osteoclastogenesis</topic><topic>Osteoclasts - cytology</topic><topic>Positive Regulatory Domain I-Binding Factor 1</topic><topic>RANK Ligand - antagonists & inhibitors</topic><topic>RANK Ligand - physiology</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RECEPTORS</topic><topic>REGULATIONS</topic><topic>Signal Transduction</topic><topic>STIMULATION</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kiyomiya, Hiroyasu</creatorcontrib><creatorcontrib>Ariyoshi, Wataru</creatorcontrib><creatorcontrib>Okinaga, Toshinori</creatorcontrib><creatorcontrib>Kaneuji, Takeshi</creatorcontrib><creatorcontrib>Mitsugi, Sho</creatorcontrib><creatorcontrib>Sakurai, Takuma</creatorcontrib><creatorcontrib>Habu, Manabu</creatorcontrib><creatorcontrib>Yoshioka, Izumi</creatorcontrib><creatorcontrib>Tominaga, Kazuhiro</creatorcontrib><creatorcontrib>Nishihara, Tatsuji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kiyomiya, Hiroyasu</au><au>Ariyoshi, Wataru</au><au>Okinaga, Toshinori</au><au>Kaneuji, Takeshi</au><au>Mitsugi, Sho</au><au>Sakurai, Takuma</au><au>Habu, Manabu</au><au>Yoshioka, Izumi</au><au>Tominaga, Kazuhiro</au><au>Nishihara, Tatsuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2015-05-01</date><risdate>2015</risdate><volume>460</volume><issue>2</issue><spage>320</spage><epage>326</epage><pages>320-326</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression.
•IL-33 inhibits RANKL-induced osteoclast formation.•IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression.•IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25795135</pmid><doi>10.1016/j.bbrc.2015.03.033</doi><tpages>7</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES ACID PHOSPHATASE Animals Base Sequence Blimp-1 BONE MARROW CELLS CATHEPSINS Cell Line Cells, Cultured CESIUM FLUORIDES DNA Primers Female GENES IL-33 IN VITRO INHIBITION INTERFERON Interferon Regulatory Factors - genetics Interferon Regulatory Factors - metabolism Interleukin-33 Interleukins - physiology IRF-8 LIGANDS LYMPHOCYTES MACROPHAGES Male MICE MONOCYTES NFATC Transcription Factors - genetics NFATC Transcription Factors - metabolism Osteoclastogenesis Osteoclasts - cytology Positive Regulatory Domain I-Binding Factor 1 RANK Ligand - antagonists & inhibitors RANK Ligand - physiology Real-Time Polymerase Chain Reaction RECEPTORS REGULATIONS Signal Transduction STIMULATION Transcription Factors - genetics Transcription Factors - metabolism |
| title | IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression |
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