FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages
Objective Asthma, a well-known disease with high morbidity, is characterized by chronic airway inflammation. However, the allergic inflammation mechanisms of follistatin-like protein 1 (FSTL1) have not been elucidated. This study aims to investigate the effects of FSTL1 in ovalbumin (OVA)-induced mi...
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| Veröffentlicht in: | Inflammation research 2021-07, Vol.70 (7), p.777-787 |
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| creator | Wang, Yan Zhang, Dong Liu, Tian Wang, Jun-fei Wu, Jin-xiang Zhao, Ji-ping Xu, Jia-wei Zhang, Jin-tao Dong, Liang |
| description | Objective
Asthma, a well-known disease with high morbidity, is characterized by chronic airway inflammation. However, the allergic inflammation mechanisms of follistatin-like protein 1 (FSTL1) have not been elucidated. This study aims to investigate the effects of FSTL1 in ovalbumin (OVA)-induced mice and macrophages on nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway.
Methods
Mice were randomly divided into control-WT, OVA-WT, control-
Fstl1
±
, OVA-
Fstl1
±
. Histological changes were assessed by HE and PAS staining. The protein levels of Muc-5AC, FSTL1, NLRP3, and IL-1β in lung tissue were detected by immunohistochemistry and ELISA. The bronchoalveolar lavage fluid (BALF) in mice and human serum samples were detected by ELISA. Then, mice were grouped into control, FSTL1, MCC950 + FSTL1 to further investigate the relationship between FSTL1 and NLRP3/IL-1β. Alveolar macrophage cells (MH-S cells) were separated into control, OVA, FSTL1, OVA + FSTL1, OVA + siNC, OVA + siFSTL1, MCC950, and FSTL1 + MCC950 groups to explore the effect of FSTL1 on the NLRP3/IL-1β signaling. The protein expression of NLRP3 and IL-1β in MH-S cells was detected by Western blot analysis.
Results
The present results uncovered that
Fstl1
±
significantly ameliorated OVA-induced Muc-5AC production and mucus hypersecretion.
Fstl1
±
was also found to decrease the production of inflammatory cytokines and inflammatory cell infiltration in OVA-induced asthmatic mice. Meanwhile, the serum concentrations of FSTL1 and IL-1β were higher in asthma subjects than the health subjects, and
Fstl1
±
ameliorated the production of NLRP3 and IL-1β in OVA-induced asthmatic mice. Furthermore, mice by injected FSTL1 substantially stimulated the expression of NLRP3 and IL-1β, while pretreatment with MCC950 in mice significantly weakened the production of NLRP3 and IL-1β induced by injection FSTL1. Pretreatment with siFSTL1 or MCC950 significantly reduced the production of NLRP3 and IL-1β induced by OVA or FSTL1 in MH-S cells.
Conclusions
The study results showed that FSTL1 played an important role in allergic airway inflammation by activating NLRP3/IL-1β. Hence, inhibition FSTL1 could be applied as a therapeutic agent against asthma. |
| doi_str_mv | 10.1007/s00011-021-01475-w |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2536483783</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2550948847</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-9b0ba65f1cf64143b66a59173324ee59eed610f9c3e32ad4cf559bfaf3ec0f3e3</originalsourceid><addsrcrecordid>eNp9kctqFUEQhhtRTIy-gAtpcOOmTV-nZ5YhGBMYjGgUd01NT82cCXOze8bDgTyVD-Iz2ccTFVy46AvUV39RfIQ8F_y14NyeRs65EIzLdIS2hm0fkGOhJWcFz788TH8uFVO54kfkSYy3Cc9lLh-TI6W5zSy3x-Tu4uNNKSi0bYBvsGCk15_PWDfWq8eadmPTwzDAMoUdDRjnaYwJqXYU_NIlvhtbumyQvis_vFenVyUTP77T2LUj9PvSDMtmC7uUQ4fOI4WxpgP4MM0baDE-JY8a6CM-u39PyKeLNzfnl6y8fnt1flYyr6xZWFHxCjLTCN9kWmhVZRmYQlilpEY0BWKdCd4UXqGSUGvfGFNUDTQKPU-XOiGvDrlzmL6uGBc3dNFj38OI0xqdNCrTubK5SujLf9DbaQ1pnT1leKHzXNtEyQOVVokxYOPm0A0Qdk5wt3fjDm5ccuN-uXHb1PTiPnqtBqz_tPyWkQB1AGIqjS2Gv7P_E_sT5dqbSw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2550948847</pqid></control><display><type>article</type><title>FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Wang, Yan ; Zhang, Dong ; Liu, Tian ; Wang, Jun-fei ; Wu, Jin-xiang ; Zhao, Ji-ping ; Xu, Jia-wei ; Zhang, Jin-tao ; Dong, Liang</creator><creatorcontrib>Wang, Yan ; Zhang, Dong ; Liu, Tian ; Wang, Jun-fei ; Wu, Jin-xiang ; Zhao, Ji-ping ; Xu, Jia-wei ; Zhang, Jin-tao ; Dong, Liang</creatorcontrib><description>Objective
Asthma, a well-known disease with high morbidity, is characterized by chronic airway inflammation. However, the allergic inflammation mechanisms of follistatin-like protein 1 (FSTL1) have not been elucidated. This study aims to investigate the effects of FSTL1 in ovalbumin (OVA)-induced mice and macrophages on nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway.
Methods
Mice were randomly divided into control-WT, OVA-WT, control-
Fstl1
±
, OVA-
Fstl1
±
. Histological changes were assessed by HE and PAS staining. The protein levels of Muc-5AC, FSTL1, NLRP3, and IL-1β in lung tissue were detected by immunohistochemistry and ELISA. The bronchoalveolar lavage fluid (BALF) in mice and human serum samples were detected by ELISA. Then, mice were grouped into control, FSTL1, MCC950 + FSTL1 to further investigate the relationship between FSTL1 and NLRP3/IL-1β. Alveolar macrophage cells (MH-S cells) were separated into control, OVA, FSTL1, OVA + FSTL1, OVA + siNC, OVA + siFSTL1, MCC950, and FSTL1 + MCC950 groups to explore the effect of FSTL1 on the NLRP3/IL-1β signaling. The protein expression of NLRP3 and IL-1β in MH-S cells was detected by Western blot analysis.
Results
The present results uncovered that
Fstl1
±
significantly ameliorated OVA-induced Muc-5AC production and mucus hypersecretion.
Fstl1
±
was also found to decrease the production of inflammatory cytokines and inflammatory cell infiltration in OVA-induced asthmatic mice. Meanwhile, the serum concentrations of FSTL1 and IL-1β were higher in asthma subjects than the health subjects, and
Fstl1
±
ameliorated the production of NLRP3 and IL-1β in OVA-induced asthmatic mice. Furthermore, mice by injected FSTL1 substantially stimulated the expression of NLRP3 and IL-1β, while pretreatment with MCC950 in mice significantly weakened the production of NLRP3 and IL-1β induced by injection FSTL1. Pretreatment with siFSTL1 or MCC950 significantly reduced the production of NLRP3 and IL-1β induced by OVA or FSTL1 in MH-S cells.
Conclusions
The study results showed that FSTL1 played an important role in allergic airway inflammation by activating NLRP3/IL-1β. Hence, inhibition FSTL1 could be applied as a therapeutic agent against asthma.</description><identifier>ISSN: 1023-3830</identifier><identifier>EISSN: 1420-908X</identifier><identifier>DOI: 10.1007/s00011-021-01475-w</identifier><identifier>PMID: 34076707</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Aged ; Allergens - immunology ; Allergology ; Alveoli ; Animals ; Asthma ; Asthma - blood ; Asthma - immunology ; Biomedical and Life Sciences ; Biomedicine ; Bronchoalveolar Lavage Fluid - immunology ; Bronchus ; Cell Line ; Chemical compounds ; Cytokines ; Cytokines - immunology ; Dermatology ; Enzyme-linked immunosorbent assay ; Female ; Follistatin ; Follistatin-Related Proteins - genetics ; Follistatin-Related Proteins - immunology ; Furans - pharmacology ; Humans ; Hypersensitivity ; IL-1β ; Immunohistochemistry ; Immunology ; Indenes - pharmacology ; Inflammation ; Interleukins ; Leucine ; Lung - immunology ; Macrophages ; Macrophages - immunology ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Morbidity ; Neurology ; NLR Family, Pyrin Domain-Containing 3 Protein - immunology ; Nucleotides ; Original Research Paper ; Ovalbumin ; Ovalbumin - immunology ; Pharmacology ; Pharmacology/Toxicology ; Pretreatment ; Proteins ; Respiratory tract ; Respiratory tract diseases ; Rheumatology ; Signal Transduction ; Signaling ; Sulfonamides - pharmacology</subject><ispartof>Inflammation research, 2021-07, Vol.70 (7), p.777-787</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.</rights><rights>The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-9b0ba65f1cf64143b66a59173324ee59eed610f9c3e32ad4cf559bfaf3ec0f3e3</citedby><cites>FETCH-LOGICAL-c375t-9b0ba65f1cf64143b66a59173324ee59eed610f9c3e32ad4cf559bfaf3ec0f3e3</cites><orcidid>0000-0001-7707-9982</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00011-021-01475-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00011-021-01475-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34076707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Zhang, Dong</creatorcontrib><creatorcontrib>Liu, Tian</creatorcontrib><creatorcontrib>Wang, Jun-fei</creatorcontrib><creatorcontrib>Wu, Jin-xiang</creatorcontrib><creatorcontrib>Zhao, Ji-ping</creatorcontrib><creatorcontrib>Xu, Jia-wei</creatorcontrib><creatorcontrib>Zhang, Jin-tao</creatorcontrib><creatorcontrib>Dong, Liang</creatorcontrib><title>FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages</title><title>Inflammation research</title><addtitle>Inflamm. Res</addtitle><addtitle>Inflamm Res</addtitle><description>Objective
Asthma, a well-known disease with high morbidity, is characterized by chronic airway inflammation. However, the allergic inflammation mechanisms of follistatin-like protein 1 (FSTL1) have not been elucidated. This study aims to investigate the effects of FSTL1 in ovalbumin (OVA)-induced mice and macrophages on nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway.
Methods
Mice were randomly divided into control-WT, OVA-WT, control-
Fstl1
±
, OVA-
Fstl1
±
. Histological changes were assessed by HE and PAS staining. The protein levels of Muc-5AC, FSTL1, NLRP3, and IL-1β in lung tissue were detected by immunohistochemistry and ELISA. The bronchoalveolar lavage fluid (BALF) in mice and human serum samples were detected by ELISA. Then, mice were grouped into control, FSTL1, MCC950 + FSTL1 to further investigate the relationship between FSTL1 and NLRP3/IL-1β. Alveolar macrophage cells (MH-S cells) were separated into control, OVA, FSTL1, OVA + FSTL1, OVA + siNC, OVA + siFSTL1, MCC950, and FSTL1 + MCC950 groups to explore the effect of FSTL1 on the NLRP3/IL-1β signaling. The protein expression of NLRP3 and IL-1β in MH-S cells was detected by Western blot analysis.
Results
The present results uncovered that
Fstl1
±
significantly ameliorated OVA-induced Muc-5AC production and mucus hypersecretion.
Fstl1
±
was also found to decrease the production of inflammatory cytokines and inflammatory cell infiltration in OVA-induced asthmatic mice. Meanwhile, the serum concentrations of FSTL1 and IL-1β were higher in asthma subjects than the health subjects, and
Fstl1
±
ameliorated the production of NLRP3 and IL-1β in OVA-induced asthmatic mice. Furthermore, mice by injected FSTL1 substantially stimulated the expression of NLRP3 and IL-1β, while pretreatment with MCC950 in mice significantly weakened the production of NLRP3 and IL-1β induced by injection FSTL1. Pretreatment with siFSTL1 or MCC950 significantly reduced the production of NLRP3 and IL-1β induced by OVA or FSTL1 in MH-S cells.
Conclusions
The study results showed that FSTL1 played an important role in allergic airway inflammation by activating NLRP3/IL-1β. Hence, inhibition FSTL1 could be applied as a therapeutic agent against asthma.</description><subject>Aged</subject><subject>Allergens - immunology</subject><subject>Allergology</subject><subject>Alveoli</subject><subject>Animals</subject><subject>Asthma</subject><subject>Asthma - blood</subject><subject>Asthma - immunology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bronchoalveolar Lavage Fluid - immunology</subject><subject>Bronchus</subject><subject>Cell Line</subject><subject>Chemical compounds</subject><subject>Cytokines</subject><subject>Cytokines - immunology</subject><subject>Dermatology</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Follistatin</subject><subject>Follistatin-Related Proteins - genetics</subject><subject>Follistatin-Related Proteins - immunology</subject><subject>Furans - pharmacology</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>IL-1β</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Indenes - pharmacology</subject><subject>Inflammation</subject><subject>Interleukins</subject><subject>Leucine</subject><subject>Lung - immunology</subject><subject>Macrophages</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>Morbidity</subject><subject>Neurology</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - immunology</subject><subject>Nucleotides</subject><subject>Original Research Paper</subject><subject>Ovalbumin</subject><subject>Ovalbumin - immunology</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Pretreatment</subject><subject>Proteins</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>Rheumatology</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Sulfonamides - pharmacology</subject><issn>1023-3830</issn><issn>1420-908X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kctqFUEQhhtRTIy-gAtpcOOmTV-nZ5YhGBMYjGgUd01NT82cCXOze8bDgTyVD-Iz2ccTFVy46AvUV39RfIQ8F_y14NyeRs65EIzLdIS2hm0fkGOhJWcFz788TH8uFVO54kfkSYy3Cc9lLh-TI6W5zSy3x-Tu4uNNKSi0bYBvsGCk15_PWDfWq8eadmPTwzDAMoUdDRjnaYwJqXYU_NIlvhtbumyQvis_vFenVyUTP77T2LUj9PvSDMtmC7uUQ4fOI4WxpgP4MM0baDE-JY8a6CM-u39PyKeLNzfnl6y8fnt1flYyr6xZWFHxCjLTCN9kWmhVZRmYQlilpEY0BWKdCd4UXqGSUGvfGFNUDTQKPU-XOiGvDrlzmL6uGBc3dNFj38OI0xqdNCrTubK5SujLf9DbaQ1pnT1leKHzXNtEyQOVVokxYOPm0A0Qdk5wt3fjDm5ccuN-uXHb1PTiPnqtBqz_tPyWkQB1AGIqjS2Gv7P_E_sT5dqbSw</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Wang, Yan</creator><creator>Zhang, Dong</creator><creator>Liu, Tian</creator><creator>Wang, Jun-fei</creator><creator>Wu, Jin-xiang</creator><creator>Zhao, Ji-ping</creator><creator>Xu, Jia-wei</creator><creator>Zhang, Jin-tao</creator><creator>Dong, Liang</creator><general>Springer International Publishing</general><general>Springer Nature B.V</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7707-9982</orcidid></search><sort><creationdate>20210701</creationdate><title>FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages</title><author>Wang, Yan ; Zhang, Dong ; Liu, Tian ; Wang, Jun-fei ; Wu, Jin-xiang ; Zhao, Ji-ping ; Xu, Jia-wei ; Zhang, Jin-tao ; Dong, Liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-9b0ba65f1cf64143b66a59173324ee59eed610f9c3e32ad4cf559bfaf3ec0f3e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Allergens - immunology</topic><topic>Allergology</topic><topic>Alveoli</topic><topic>Animals</topic><topic>Asthma</topic><topic>Asthma - blood</topic><topic>Asthma - immunology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bronchoalveolar Lavage Fluid - immunology</topic><topic>Bronchus</topic><topic>Cell Line</topic><topic>Chemical compounds</topic><topic>Cytokines</topic><topic>Cytokines - immunology</topic><topic>Dermatology</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Follistatin</topic><topic>Follistatin-Related Proteins - genetics</topic><topic>Follistatin-Related Proteins - immunology</topic><topic>Furans - pharmacology</topic><topic>Humans</topic><topic>Hypersensitivity</topic><topic>IL-1β</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Indenes - pharmacology</topic><topic>Inflammation</topic><topic>Interleukins</topic><topic>Leucine</topic><topic>Lung - immunology</topic><topic>Macrophages</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>Morbidity</topic><topic>Neurology</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - immunology</topic><topic>Nucleotides</topic><topic>Original Research Paper</topic><topic>Ovalbumin</topic><topic>Ovalbumin - immunology</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Pretreatment</topic><topic>Proteins</topic><topic>Respiratory tract</topic><topic>Respiratory tract diseases</topic><topic>Rheumatology</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Sulfonamides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Zhang, Dong</creatorcontrib><creatorcontrib>Liu, Tian</creatorcontrib><creatorcontrib>Wang, Jun-fei</creatorcontrib><creatorcontrib>Wu, Jin-xiang</creatorcontrib><creatorcontrib>Zhao, Ji-ping</creatorcontrib><creatorcontrib>Xu, Jia-wei</creatorcontrib><creatorcontrib>Zhang, Jin-tao</creatorcontrib><creatorcontrib>Dong, Liang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</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>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</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>MEDLINE - Academic</collection><jtitle>Inflammation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yan</au><au>Zhang, Dong</au><au>Liu, Tian</au><au>Wang, Jun-fei</au><au>Wu, Jin-xiang</au><au>Zhao, Ji-ping</au><au>Xu, Jia-wei</au><au>Zhang, Jin-tao</au><au>Dong, Liang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages</atitle><jtitle>Inflammation research</jtitle><stitle>Inflamm. Res</stitle><addtitle>Inflamm Res</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>70</volume><issue>7</issue><spage>777</spage><epage>787</epage><pages>777-787</pages><issn>1023-3830</issn><eissn>1420-908X</eissn><abstract>Objective
Asthma, a well-known disease with high morbidity, is characterized by chronic airway inflammation. However, the allergic inflammation mechanisms of follistatin-like protein 1 (FSTL1) have not been elucidated. This study aims to investigate the effects of FSTL1 in ovalbumin (OVA)-induced mice and macrophages on nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway.
Methods
Mice were randomly divided into control-WT, OVA-WT, control-
Fstl1
±
, OVA-
Fstl1
±
. Histological changes were assessed by HE and PAS staining. The protein levels of Muc-5AC, FSTL1, NLRP3, and IL-1β in lung tissue were detected by immunohistochemistry and ELISA. The bronchoalveolar lavage fluid (BALF) in mice and human serum samples were detected by ELISA. Then, mice were grouped into control, FSTL1, MCC950 + FSTL1 to further investigate the relationship between FSTL1 and NLRP3/IL-1β. Alveolar macrophage cells (MH-S cells) were separated into control, OVA, FSTL1, OVA + FSTL1, OVA + siNC, OVA + siFSTL1, MCC950, and FSTL1 + MCC950 groups to explore the effect of FSTL1 on the NLRP3/IL-1β signaling. The protein expression of NLRP3 and IL-1β in MH-S cells was detected by Western blot analysis.
Results
The present results uncovered that
Fstl1
±
significantly ameliorated OVA-induced Muc-5AC production and mucus hypersecretion.
Fstl1
±
was also found to decrease the production of inflammatory cytokines and inflammatory cell infiltration in OVA-induced asthmatic mice. Meanwhile, the serum concentrations of FSTL1 and IL-1β were higher in asthma subjects than the health subjects, and
Fstl1
±
ameliorated the production of NLRP3 and IL-1β in OVA-induced asthmatic mice. Furthermore, mice by injected FSTL1 substantially stimulated the expression of NLRP3 and IL-1β, while pretreatment with MCC950 in mice significantly weakened the production of NLRP3 and IL-1β induced by injection FSTL1. Pretreatment with siFSTL1 or MCC950 significantly reduced the production of NLRP3 and IL-1β induced by OVA or FSTL1 in MH-S cells.
Conclusions
The study results showed that FSTL1 played an important role in allergic airway inflammation by activating NLRP3/IL-1β. Hence, inhibition FSTL1 could be applied as a therapeutic agent against asthma.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>34076707</pmid><doi>10.1007/s00011-021-01475-w</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7707-9982</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1023-3830 |
| ispartof | Inflammation research, 2021-07, Vol.70 (7), p.777-787 |
| issn | 1023-3830 1420-908X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2536483783 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Aged Allergens - immunology Allergology Alveoli Animals Asthma Asthma - blood Asthma - immunology Biomedical and Life Sciences Biomedicine Bronchoalveolar Lavage Fluid - immunology Bronchus Cell Line Chemical compounds Cytokines Cytokines - immunology Dermatology Enzyme-linked immunosorbent assay Female Follistatin Follistatin-Related Proteins - genetics Follistatin-Related Proteins - immunology Furans - pharmacology Humans Hypersensitivity IL-1β Immunohistochemistry Immunology Indenes - pharmacology Inflammation Interleukins Leucine Lung - immunology Macrophages Macrophages - immunology Male Mice Mice, Inbred C57BL Middle Aged Morbidity Neurology NLR Family, Pyrin Domain-Containing 3 Protein - immunology Nucleotides Original Research Paper Ovalbumin Ovalbumin - immunology Pharmacology Pharmacology/Toxicology Pretreatment Proteins Respiratory tract Respiratory tract diseases Rheumatology Signal Transduction Signaling Sulfonamides - pharmacology |
| title | FSTL1 aggravates OVA-induced inflammatory responses by activating the NLRP3/IL-1β signaling pathway in mice and macrophages |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T01%3A57%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=FSTL1%20aggravates%20OVA-induced%20inflammatory%20responses%20by%20activating%20the%20NLRP3/IL-1%CE%B2%20signaling%20pathway%20in%20mice%20and%20macrophages&rft.jtitle=Inflammation%20research&rft.au=Wang,%20Yan&rft.date=2021-07-01&rft.volume=70&rft.issue=7&rft.spage=777&rft.epage=787&rft.pages=777-787&rft.issn=1023-3830&rft.eissn=1420-908X&rft_id=info:doi/10.1007/s00011-021-01475-w&rft_dat=%3Cproquest_cross%3E2550948847%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2550948847&rft_id=info:pmid/34076707&rfr_iscdi=true |