IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways
Keloid is an abnormal fibrotic disease after cutaneous injury characterized by exaggerated scar tissue formation, which often extends beyond the boundaries of the original wound. Although chronic inflammation is known to be associated with the excessive inflammation in keloid tissue, there are few s...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.888719/full |
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| author | Seon-Yeong Lee A Ram Lee A Ram Lee Jeong Won Choi Chae Rim Lee Chae Rim Lee Keun-Hyung Cho Keun-Hyung Cho Jung Ho Lee Mi-La Cho Mi-La Cho |
| author_facet | Seon-Yeong Lee A Ram Lee A Ram Lee Jeong Won Choi Chae Rim Lee Chae Rim Lee Keun-Hyung Cho Keun-Hyung Cho Jung Ho Lee Mi-La Cho Mi-La Cho |
| author_sort | Seon-Yeong Lee |
| collection | DOAJ |
| description | Keloid is an abnormal fibrotic disease after cutaneous injury characterized by exaggerated scar tissue formation, which often extends beyond the boundaries of the original wound. Although chronic inflammation is known to be associated with the excessive inflammation in keloid tissue, there are few studies on the role of autophagy in the pathogenesis of keloid. In this study, we evaluated the pattern of autophagy in keloid fibroblasts (KF) and normal fibroblasts (NF). Expression of HIF-1α, STAT3 and autophagic flux markers were evaluated in KF and NF. Defective autophagy caused by IL-17 was evaluated, and the relationship between defective autophagy and necroptosis was also examined. The expression of IL-17, HIF-1α and STAT3 was significantly increased in keloid tissue, and autophagosome-to autophagolysosome conversion was defective in KF. IL-17 treatment significantly elevated the expression of STAT3 and HIF-1α in NF and caused defective autophagy, which was reversed by HIF-1α inhibitor. In addition, the defective autophagy was associated with the increased necroptosis and fibrosis. In keloid tissue, the elevated necroptosis marker was confirmed, and with the HIF-1α inhibitor, the defective autophagy, necroptosis and fibrosis was decreased in KF. In conclusion, autophagy was defective in keloid tissue, which was associated with increased necroptosis and fibrosis. The IL-17-STAT3-HIF-1α axis was involved in defective autophagy in KF, and this suggests that targeting the axis could alleviate chronic inflammation in keloid disease. |
| first_indexed | 2024-04-13T21:46:05Z |
| format | Article |
| id | doaj.art-29309d90daa54abda9e3c95b30c4f70e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T21:46:05Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-29309d90daa54abda9e3c95b30c4f70e2022-12-22T02:28:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.888719888719IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling PathwaysSeon-Yeong Lee0A Ram Lee1A Ram Lee2Jeong Won Choi3Chae Rim Lee4Chae Rim Lee5Keun-Hyung Cho6Keun-Hyung Cho7Jung Ho Lee8Mi-La Cho9Mi-La Cho10Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Plastic and Reconstructive Surgery, College of Medicine, The Catholic University of Korea, Seoul, South KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaDepartment of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, South KoreaKeloid is an abnormal fibrotic disease after cutaneous injury characterized by exaggerated scar tissue formation, which often extends beyond the boundaries of the original wound. Although chronic inflammation is known to be associated with the excessive inflammation in keloid tissue, there are few studies on the role of autophagy in the pathogenesis of keloid. In this study, we evaluated the pattern of autophagy in keloid fibroblasts (KF) and normal fibroblasts (NF). Expression of HIF-1α, STAT3 and autophagic flux markers were evaluated in KF and NF. Defective autophagy caused by IL-17 was evaluated, and the relationship between defective autophagy and necroptosis was also examined. The expression of IL-17, HIF-1α and STAT3 was significantly increased in keloid tissue, and autophagosome-to autophagolysosome conversion was defective in KF. IL-17 treatment significantly elevated the expression of STAT3 and HIF-1α in NF and caused defective autophagy, which was reversed by HIF-1α inhibitor. In addition, the defective autophagy was associated with the increased necroptosis and fibrosis. In keloid tissue, the elevated necroptosis marker was confirmed, and with the HIF-1α inhibitor, the defective autophagy, necroptosis and fibrosis was decreased in KF. In conclusion, autophagy was defective in keloid tissue, which was associated with increased necroptosis and fibrosis. The IL-17-STAT3-HIF-1α axis was involved in defective autophagy in KF, and this suggests that targeting the axis could alleviate chronic inflammation in keloid disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.888719/fullkeloidautophagic fluxIL-17stat3HIF-1α |
| spellingShingle | Seon-Yeong Lee A Ram Lee A Ram Lee Jeong Won Choi Chae Rim Lee Chae Rim Lee Keun-Hyung Cho Keun-Hyung Cho Jung Ho Lee Mi-La Cho Mi-La Cho IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways Frontiers in Immunology keloid autophagic flux IL-17 stat3 HIF-1α |
| title | IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways |
| title_full | IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways |
| title_fullStr | IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways |
| title_full_unstemmed | IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways |
| title_short | IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways |
| title_sort | il 17 induces autophagy dysfunction to promote inflammatory cell death and fibrosis in keloid fibroblasts via the stat3 and hif 1α dependent signaling pathways |
| topic | keloid autophagic flux IL-17 stat3 HIF-1α |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.888719/full |
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