Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis

We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and ca...

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Main Authors: Lingxiao Xu, Qiuyue Peng, Wenhua Xuan, Xiaoke Feng, Xiangqing Kong, Miaojia Zhang, Wenfeng Tan, Meilang Xue, Fang Wang
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/9631510
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author Lingxiao Xu
Qiuyue Peng
Wenhua Xuan
Xiaoke Feng
Xiangqing Kong
Miaojia Zhang
Wenfeng Tan
Meilang Xue
Fang Wang
author_facet Lingxiao Xu
Qiuyue Peng
Wenhua Xuan
Xiaoke Feng
Xiangqing Kong
Miaojia Zhang
Wenfeng Tan
Meilang Xue
Fang Wang
author_sort Lingxiao Xu
collection DOAJ
description We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.
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spelling doaj-art-77d5db9c8d5742b5b7f0ad18be0ac4332025-02-03T07:24:19ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/96315109631510Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in OsteoarthritisLingxiao Xu0Qiuyue Peng1Wenhua Xuan2Xiaoke Feng3Xiangqing Kong4Miaojia Zhang5Wenfeng Tan6Meilang Xue7Fang Wang8Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaSutton Arthritis Research Laboratories, University of Sydney at Royal North Shore Hospital, Sydney, NSW, AustraliaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaWe have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.http://dx.doi.org/10.1155/2016/9631510
spellingShingle Lingxiao Xu
Qiuyue Peng
Wenhua Xuan
Xiaoke Feng
Xiangqing Kong
Miaojia Zhang
Wenfeng Tan
Meilang Xue
Fang Wang
Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis
Mediators of Inflammation
title Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis
title_full Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis
title_fullStr Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis
title_full_unstemmed Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis
title_short Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis
title_sort interleukin 29 enhances synovial inflammation and cartilage degradation in osteoarthritis
url http://dx.doi.org/10.1155/2016/9631510
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