IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice
Abstract Background Interstitial lung disease, a common extra-articular complication of connective tissue disease, is characterized by progressive and irreversible pulmonary inflammation and fibrosis, which causes significant mortality. IL-22 shows a potential in regulating chronic inflammation and...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02977-6 |
| _version_ | 1828086966116155392 |
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| author | Ziye Qu Wencan Dou Kexin Zhang Lili Duan Dongmei Zhou Songlou Yin |
| author_facet | Ziye Qu Wencan Dou Kexin Zhang Lili Duan Dongmei Zhou Songlou Yin |
| author_sort | Ziye Qu |
| collection | DOAJ |
| description | Abstract Background Interstitial lung disease, a common extra-articular complication of connective tissue disease, is characterized by progressive and irreversible pulmonary inflammation and fibrosis, which causes significant mortality. IL-22 shows a potential in regulating chronic inflammation and possibly plays an anti-fibrotic role by protecting epithelial cells. However, the detailed effects and underlying mechanisms are still unclear. In this study, we explored the impact of IL-22 on pulmonary fibrosis both in vivo and in vitro. Methods To induce pulmonary fibrosis, wild-type mice and IL-22 knockout mice were intratracheally injected with bleomycin followed by treatments with recombinant IL-22 or IL-17A neutralizing antibody. We investigated the role of IL-22 on bleomycin-induced pulmonary fibrosis and the mechanism in the possible interaction between IL-22 and IL-17A. Fibrosis-related genes were detected using RT-qPCR, western blot, and immunofluorescence. Inflammatory and fibrotic changes were assessed based on histological features. We also used A549 human alveolar epithelial cells, NIH/3T3 mouse fibroblast cells, and primary mouse lung fibroblasts to study the impact of IL-22 on fibrosis in vitro. Results IL-22 knockout mice showed aggravated pulmonary fibrosis compared with wild-type mice, and injection of recombinant IL-22 decreased the severe fibrotic manifestations in IL-22 knockout mice. In cell culture assays, IL-22 decreased protein levels of Collagen I in A549 cells, NIH/3T3 cells, and primary mouse lung fibroblasts. IL-22 also reduced the protein level of Collagen I in NIH/3T3 cells which were co-cultured with T cells. Mechanistically, IL-22 reduced the Th17 cell proportion and IL-17A mRNA level in lung tissues, and treatment with an IL-17A neutralizing antibody alleviated the severe pulmonary fibrosis in IL-22 knockout mice. The IL-17A neutralizing antibody also reduced Collagen I expression in NIH/3T3 cells in vitro. Knockdown of IL-17A with siRNAs or administration of IL-22 in NIH/3T3 cells and MLFs decreased expression of Collagen I, an effect blocked by concurrent use of recombinant IL-17A. Conclusions IL-22 mediated an anti-fibrogenesis effect in the bleomycin-induced pulmonary fibrosis model and this effect was associated with inhibition of IL-17A. |
| first_indexed | 2024-04-11T05:05:30Z |
| format | Article |
| id | doaj.art-a70b4159a7e54f1d84cc9ffb96489b46 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-11T05:05:30Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-a70b4159a7e54f1d84cc9ffb96489b462022-12-25T12:24:20ZengBMCArthritis Research & Therapy1478-63622022-12-0124111410.1186/s13075-022-02977-6IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in miceZiye Qu0Wencan Dou1Kexin Zhang2Lili Duan3Dongmei Zhou4Songlou Yin5Department of Rheumatology, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of Rheumatology, The Affiliated Hospital of Xuzhou Medical UniversityBlood Diseases Institute, Xuzhou Medical UniversityDepartment of Rheumatology, The People’s Hospital of Jiawang District of XuzhouDepartment of Rheumatology, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of Rheumatology, The Affiliated Hospital of Xuzhou Medical UniversityAbstract Background Interstitial lung disease, a common extra-articular complication of connective tissue disease, is characterized by progressive and irreversible pulmonary inflammation and fibrosis, which causes significant mortality. IL-22 shows a potential in regulating chronic inflammation and possibly plays an anti-fibrotic role by protecting epithelial cells. However, the detailed effects and underlying mechanisms are still unclear. In this study, we explored the impact of IL-22 on pulmonary fibrosis both in vivo and in vitro. Methods To induce pulmonary fibrosis, wild-type mice and IL-22 knockout mice were intratracheally injected with bleomycin followed by treatments with recombinant IL-22 or IL-17A neutralizing antibody. We investigated the role of IL-22 on bleomycin-induced pulmonary fibrosis and the mechanism in the possible interaction between IL-22 and IL-17A. Fibrosis-related genes were detected using RT-qPCR, western blot, and immunofluorescence. Inflammatory and fibrotic changes were assessed based on histological features. We also used A549 human alveolar epithelial cells, NIH/3T3 mouse fibroblast cells, and primary mouse lung fibroblasts to study the impact of IL-22 on fibrosis in vitro. Results IL-22 knockout mice showed aggravated pulmonary fibrosis compared with wild-type mice, and injection of recombinant IL-22 decreased the severe fibrotic manifestations in IL-22 knockout mice. In cell culture assays, IL-22 decreased protein levels of Collagen I in A549 cells, NIH/3T3 cells, and primary mouse lung fibroblasts. IL-22 also reduced the protein level of Collagen I in NIH/3T3 cells which were co-cultured with T cells. Mechanistically, IL-22 reduced the Th17 cell proportion and IL-17A mRNA level in lung tissues, and treatment with an IL-17A neutralizing antibody alleviated the severe pulmonary fibrosis in IL-22 knockout mice. The IL-17A neutralizing antibody also reduced Collagen I expression in NIH/3T3 cells in vitro. Knockdown of IL-17A with siRNAs or administration of IL-22 in NIH/3T3 cells and MLFs decreased expression of Collagen I, an effect blocked by concurrent use of recombinant IL-17A. Conclusions IL-22 mediated an anti-fibrogenesis effect in the bleomycin-induced pulmonary fibrosis model and this effect was associated with inhibition of IL-17A.https://doi.org/10.1186/s13075-022-02977-6IL-22BleomycinPulmonary fibrosisIL-17A |
| spellingShingle | Ziye Qu Wencan Dou Kexin Zhang Lili Duan Dongmei Zhou Songlou Yin IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice Arthritis Research & Therapy IL-22 Bleomycin Pulmonary fibrosis IL-17A |
| title | IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice |
| title_full | IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice |
| title_fullStr | IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice |
| title_full_unstemmed | IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice |
| title_short | IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice |
| title_sort | il 22 inhibits bleomycin induced pulmonary fibrosis in association with inhibition of il 17a in mice |
| topic | IL-22 Bleomycin Pulmonary fibrosis IL-17A |
| url | https://doi.org/10.1186/s13075-022-02977-6 |
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