IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus

Interleukin- (IL-) 33 contributes to various inflammatory processes. IL-33/ST2 activation participates in systemic lupus erythematous via binding to the receptor of Suppression of Tumorigenicity 2 protein (ST2). However, whether IL-33/ST2 interferes with the nosogenesis of cutaneous lupus erythemato...

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Main Authors: Yitian Song, Fangzhi Wei, Ying Liu, Feng Han, Lihui Ma, Yanping Zhuang, Chengdan Pan, Zhandong Jia, Aimin Gong
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2022/4955761
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author Yitian Song
Fangzhi Wei
Ying Liu
Feng Han
Lihui Ma
Yanping Zhuang
Chengdan Pan
Zhandong Jia
Aimin Gong
author_facet Yitian Song
Fangzhi Wei
Ying Liu
Feng Han
Lihui Ma
Yanping Zhuang
Chengdan Pan
Zhandong Jia
Aimin Gong
author_sort Yitian Song
collection DOAJ
description Interleukin- (IL-) 33 contributes to various inflammatory processes. IL-33/ST2 activation participates in systemic lupus erythematous via binding to the receptor of Suppression of Tumorigenicity 2 protein (ST2). However, whether IL-33/ST2 interferes with the nosogenesis of cutaneous lupus erythematosus (CLE) has not been reported so far. Herein, we proposed to disclose the impacts on IL-33/ST2 activation and Ro60 on CLE and their potential implications in the photosensitization of CLE cells. IL-33, ST2, and Ro60 in CLE patients’ skin lesions were detected. Murine keratinocytes stimulated with or without IL-33 were irradiated by ultraviolet B (UVB), and the levels of Ro60 and inflammation markers were determined. Keratinocytes were cocultured with J774.2 macrophages and stimulated with IL-33 for analysis of chemostasis. The results identified that IL-33, ST2, and downstream inflammation markers were significantly upregulated in CLE lesions with Ro60 overexpression. Additionally, IL-33 treatment promoted the upregulation of Ro60 induced by UVB treatment in murine keratinocytes. Moreover, IL-33 stimulates keratinocytes to induce macrophage migration via enhancing the generation of the chemokine (C–C motif) ligands 17 and 22. Meanwhile, the silencing of ST2 or nuclear factor-kappa B (NF-κB) suppression abolished IL-33-induced upregulation of Ro60 in keratinocytes. Similarly, the inhibition of SOX17 expression was followed by downregulation of Ro60 in keratinocytes following IL-33 stimulation. In addition, UVB irradiation upregulated SOX17 in keratinocytes. Conclusively, the IL-33/ST2 axis interferes with Ro60-regulated photosensitization via activating the NF-κB- and PI3K/Akt- and SOX17-related pathways.
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spelling doaj-art-8eee6095667540d5a5d6f433814cac832025-02-03T05:49:22ZengWileyMediators of Inflammation1466-18612022-01-01202210.1155/2022/4955761IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus ErythematosusYitian Song0Fangzhi Wei1Ying Liu2Feng Han3Lihui Ma4Yanping Zhuang5Chengdan Pan6Zhandong Jia7Aimin Gong8Department of Internal Medicine of Traditional Chinese MedicineDepartment of Internal Medicine of Traditional Chinese MedicineDepartment of Rheumatology and ImmunologyDepartment of Laboratory MedicineDepartment of Rheumatology and ImmunologyDepartment of Internal Medicine of Traditional Chinese MedicineDepartment of Internal Medicine of Traditional Chinese MedicineDepartment of NephrologyDepartment of Internal Medicine of Traditional Chinese MedicineInterleukin- (IL-) 33 contributes to various inflammatory processes. IL-33/ST2 activation participates in systemic lupus erythematous via binding to the receptor of Suppression of Tumorigenicity 2 protein (ST2). However, whether IL-33/ST2 interferes with the nosogenesis of cutaneous lupus erythematosus (CLE) has not been reported so far. Herein, we proposed to disclose the impacts on IL-33/ST2 activation and Ro60 on CLE and their potential implications in the photosensitization of CLE cells. IL-33, ST2, and Ro60 in CLE patients’ skin lesions were detected. Murine keratinocytes stimulated with or without IL-33 were irradiated by ultraviolet B (UVB), and the levels of Ro60 and inflammation markers were determined. Keratinocytes were cocultured with J774.2 macrophages and stimulated with IL-33 for analysis of chemostasis. The results identified that IL-33, ST2, and downstream inflammation markers were significantly upregulated in CLE lesions with Ro60 overexpression. Additionally, IL-33 treatment promoted the upregulation of Ro60 induced by UVB treatment in murine keratinocytes. Moreover, IL-33 stimulates keratinocytes to induce macrophage migration via enhancing the generation of the chemokine (C–C motif) ligands 17 and 22. Meanwhile, the silencing of ST2 or nuclear factor-kappa B (NF-κB) suppression abolished IL-33-induced upregulation of Ro60 in keratinocytes. Similarly, the inhibition of SOX17 expression was followed by downregulation of Ro60 in keratinocytes following IL-33 stimulation. In addition, UVB irradiation upregulated SOX17 in keratinocytes. Conclusively, the IL-33/ST2 axis interferes with Ro60-regulated photosensitization via activating the NF-κB- and PI3K/Akt- and SOX17-related pathways.http://dx.doi.org/10.1155/2022/4955761
spellingShingle Yitian Song
Fangzhi Wei
Ying Liu
Feng Han
Lihui Ma
Yanping Zhuang
Chengdan Pan
Zhandong Jia
Aimin Gong
IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus
Mediators of Inflammation
title IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus
title_full IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus
title_fullStr IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus
title_full_unstemmed IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus
title_short IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus
title_sort il 33 st2 activation is involved in ro60 regulated photosensitivity in cutaneous lupus erythematosus
url http://dx.doi.org/10.1155/2022/4955761
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