Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway
IntroductionPulmonary fibrosis (PF) is a fatal pathological subtype of interstitial lung disease, frequently manifests as a pulmonary complication of connective tissue disease. Iguratimod (IGU) is a new class of anti-rheumatic drugs used in the treatment of rheumatoid arthritis (RA). Studies have re...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1558903/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850053050964639744 |
|---|---|
| author | Huan Xu Huan Xu Kaixuan Ma Kaixuan Ma Ziting Ma Ziting Ma Tianyu Zhuang Tianyu Zhuang Ling Lin Ling Lin |
| author_facet | Huan Xu Huan Xu Kaixuan Ma Kaixuan Ma Ziting Ma Ziting Ma Tianyu Zhuang Tianyu Zhuang Ling Lin Ling Lin |
| author_sort | Huan Xu |
| collection | DOAJ |
| description | IntroductionPulmonary fibrosis (PF) is a fatal pathological subtype of interstitial lung disease, frequently manifests as a pulmonary complication of connective tissue disease. Iguratimod (IGU) is a new class of anti-rheumatic drugs used in the treatment of rheumatoid arthritis (RA). Studies have reported that RA patients treated with IGU have better lung function, and IGU effectively ameliorates PF. However, the mechanism by which IGU improves PF is still unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of IGU in PF through in vivo and in vitro investigations, so as to provide a new treatment method for PF.MethodsIn our research, bleomycin (BLM)-induced PF of mice were used to observe the therapeutic effect of different concentrations of IGU. And the effects of IGU on macrophage polarization and activation pathway TLR4/NF-κB in lung tissue were analyzed. In addition, Raw264.7 macrophages were induced to M1 and M2 polarization in vitro, and the effects of IGU on Raw264.7 macrophage polarization and related pathways were observed.ResultsIn our study, database analysis suggested that macrophage polarization-relative genes and pathways as well as TLR4 activation played important roles in BLM-induced PF in mice. Besides, we found that IGU effectively ameliorated BLM-induced PF and epithelial-mesenchymal transition in mice, and inhibited the polarization of M1/M2 macrophages at different stages of PF. Moreover, In vitro studies further demonstrated that IGU suppressed M1 polarization of Raw264.7 and its activation pathway TLR4/NF-κB.DiscussionIn summary, IGU inhibits the activation of macrophages and M1 polarization through inhibiting the TLR4/NF-κB pathway, thereby improving BLM-induced pulmonary inflammation and fibrosis in mice. It is suggested that IGU may be a new therapeutic option for interstitial pulmonary fibrosis. |
| format | Article |
| id | doaj-art-eefc987efbef480f98376fada9cbf6d6 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-eefc987efbef480f98376fada9cbf6d62025-08-20T02:52:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15589031558903Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathwayHuan Xu0Huan Xu1Kaixuan Ma2Kaixuan Ma3Ziting Ma4Ziting Ma5Tianyu Zhuang6Tianyu Zhuang7Ling Lin8Ling Lin9Department of Rheumatology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaLaboratory of Molecular Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Rheumatology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaLaboratory of Molecular Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaLaboratory of Molecular Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Gastroenterology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaLaboratory of Molecular Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Endocrinology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Rheumatology, First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Rheumatology, Shantou University Medical College, Shantou, ChinaIntroductionPulmonary fibrosis (PF) is a fatal pathological subtype of interstitial lung disease, frequently manifests as a pulmonary complication of connective tissue disease. Iguratimod (IGU) is a new class of anti-rheumatic drugs used in the treatment of rheumatoid arthritis (RA). Studies have reported that RA patients treated with IGU have better lung function, and IGU effectively ameliorates PF. However, the mechanism by which IGU improves PF is still unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of IGU in PF through in vivo and in vitro investigations, so as to provide a new treatment method for PF.MethodsIn our research, bleomycin (BLM)-induced PF of mice were used to observe the therapeutic effect of different concentrations of IGU. And the effects of IGU on macrophage polarization and activation pathway TLR4/NF-κB in lung tissue were analyzed. In addition, Raw264.7 macrophages were induced to M1 and M2 polarization in vitro, and the effects of IGU on Raw264.7 macrophage polarization and related pathways were observed.ResultsIn our study, database analysis suggested that macrophage polarization-relative genes and pathways as well as TLR4 activation played important roles in BLM-induced PF in mice. Besides, we found that IGU effectively ameliorated BLM-induced PF and epithelial-mesenchymal transition in mice, and inhibited the polarization of M1/M2 macrophages at different stages of PF. Moreover, In vitro studies further demonstrated that IGU suppressed M1 polarization of Raw264.7 and its activation pathway TLR4/NF-κB.DiscussionIn summary, IGU inhibits the activation of macrophages and M1 polarization through inhibiting the TLR4/NF-κB pathway, thereby improving BLM-induced pulmonary inflammation and fibrosis in mice. It is suggested that IGU may be a new therapeutic option for interstitial pulmonary fibrosis.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1558903/fullinterstitial pulmonary fibrosisinflammationiguratimodM1 polarizationTLR4 |
| spellingShingle | Huan Xu Huan Xu Kaixuan Ma Kaixuan Ma Ziting Ma Ziting Ma Tianyu Zhuang Tianyu Zhuang Ling Lin Ling Lin Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway Frontiers in Immunology interstitial pulmonary fibrosis inflammation iguratimod M1 polarization TLR4 |
| title | Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway |
| title_full | Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway |
| title_fullStr | Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway |
| title_full_unstemmed | Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway |
| title_short | Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway |
| title_sort | iguratimod improves bleomycin induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the tlr4 nf κb pathway |
| topic | interstitial pulmonary fibrosis inflammation iguratimod M1 polarization TLR4 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1558903/full |
| work_keys_str_mv | AT huanxu iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT huanxu iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT kaixuanma iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT kaixuanma iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT zitingma iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT zitingma iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT tianyuzhuang iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT tianyuzhuang iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT linglin iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway AT linglin iguratimodimprovesbleomycininducedpulmonaryinflammationandfibrosisbyregulatingmacrophagepolarizationthroughinhibitingthetlr4nfkbpathway |