IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression. In this study, we aimed to exp...

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Main Authors: Bing Wang, Zijian Ma, Miaomiao Wang, Xiaotong Sun, Yawei Tang, Ming Li, Yan Zhang, Fang Li, Xia Li
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2017/1567120
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author Bing Wang
Zijian Ma
Miaomiao Wang
Xiaotong Sun
Yawei Tang
Ming Li
Yan Zhang
Fang Li
Xia Li
author_facet Bing Wang
Zijian Ma
Miaomiao Wang
Xiaotong Sun
Yawei Tang
Ming Li
Yan Zhang
Fang Li
Xia Li
author_sort Bing Wang
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression. In this study, we aimed to explore the effect of interleukin-34 (IL-34) on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17. We found that serum IL-34 levels were increased compared to those of the healthy controls and had positive correlations with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide (CCP) antibody accordingly. CSF-1R was also highly expressed on RA FLS. The interaction of IL-34 and CSF-1R promoted a dramatic production of IL-6 by FLS through JNK/P38/NF-κB signaling pathway. Further, the IL-34-stimulated IL-6 secretion by RA FLS was found to upregulate the number of Th17. The treatment of IL-6R antagonist could attenuate the production of Th17 mediated by IL-34-stimulated RA FLS. Our results suggest that the increased IL-34 levels were closely related to the disease activity of RA. Additionally, the overexpression of IL-6 in the IL-34-stimulated FLS promoted the generation of Th17. Therefore, IL-34 was supposed to be involved in the pathogenesis of RA. The inhibition of IL-34 might provide a novel target for therapies of RA.
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spelling doaj-art-b3cbb2da3df84fe98d0798e60b35ac6c2025-08-20T03:20:51ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/15671201567120IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like SynoviocytesBing Wang0Zijian Ma1Miaomiao Wang2Xiaotong Sun3Yawei Tang4Ming Li5Yan Zhang6Fang Li7Xia Li8Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, ChinaDepartment of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Hebei Medical University, Hebei, ChinaDepartment of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, ChinaDepartment of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, ChinaDepartment of Microecology, College of Basic Medical Science, Dalian Medical University, Liaoning, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning, ChinaDepartment of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, ChinaDepartment of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning, ChinaRheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression. In this study, we aimed to explore the effect of interleukin-34 (IL-34) on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17. We found that serum IL-34 levels were increased compared to those of the healthy controls and had positive correlations with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide (CCP) antibody accordingly. CSF-1R was also highly expressed on RA FLS. The interaction of IL-34 and CSF-1R promoted a dramatic production of IL-6 by FLS through JNK/P38/NF-κB signaling pathway. Further, the IL-34-stimulated IL-6 secretion by RA FLS was found to upregulate the number of Th17. The treatment of IL-6R antagonist could attenuate the production of Th17 mediated by IL-34-stimulated RA FLS. Our results suggest that the increased IL-34 levels were closely related to the disease activity of RA. Additionally, the overexpression of IL-6 in the IL-34-stimulated FLS promoted the generation of Th17. Therefore, IL-34 was supposed to be involved in the pathogenesis of RA. The inhibition of IL-34 might provide a novel target for therapies of RA.http://dx.doi.org/10.1155/2017/1567120
spellingShingle Bing Wang
Zijian Ma
Miaomiao Wang
Xiaotong Sun
Yawei Tang
Ming Li
Yan Zhang
Fang Li
Xia Li
IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes
Mediators of Inflammation
title IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes
title_full IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes
title_fullStr IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes
title_full_unstemmed IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes
title_short IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes
title_sort il 34 upregulated th17 production through increased il 6 expression by rheumatoid fibroblast like synoviocytes
url http://dx.doi.org/10.1155/2017/1567120
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