PMID- 27433031 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20231213 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2016 DP - 2016 TI - Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis. PG - 9631510 LID - 10.1155/2016/9631510 [doi] LID - 9631510 AB - 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-1beta, 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-kappaB (NF-kappaB), 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. FAU - Xu, Lingxiao AU - Xu L AD - Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Peng, Qiuyue AU - Peng Q AD - Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Xuan, Wenhua AU - Xuan W AD - Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Feng, Xiaoke AU - Feng X AD - Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Kong, Xiangqing AU - Kong X AUID- ORCID: 0000-0002-5433-5557 AD - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Zhang, Miaojia AU - Zhang M AD - Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Tan, Wenfeng AU - Tan W AD - Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Xue, Meilang AU - Xue M AD - Sutton Arthritis Research Laboratories, University of Sydney at Royal North Shore Hospital, Sydney, NSW, Australia. FAU - Wang, Fang AU - Wang F AUID- ORCID: 0000-0002-0526-7607 AD - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. LA - eng PT - Journal Article DEP - 20160628 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (interferon-lambda, human) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Interleukins) RN - 0 (Receptors, Cytokine) RN - 0 (interleukin 28alpha receptor) RN - 9008-11-1 (Interferons) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Aged MH - Cartilage/immunology/*metabolism/pathology MH - Cells, Cultured MH - Female MH - Fibroblasts/immunology/metabolism MH - Flow Cytometry MH - Humans MH - In Vitro Techniques MH - Inflammation/immunology/metabolism MH - Interferons MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Interleukin-8/metabolism MH - Interleukins/genetics/*metabolism MH - Leukocytes, Mononuclear/metabolism MH - Male MH - Matrix Metalloproteinase 3/metabolism MH - Middle Aged MH - Osteoarthritis/*metabolism/*pathology MH - Receptors, Cytokine/genetics/metabolism MH - Signal Transduction MH - Synovial Fluid/cytology/immunology/*metabolism PMC - PMC4940582 EDAT- 2016/07/20 06:00 MHDA- 2017/05/16 06:00 PMCR- 2016/06/28 CRDT- 2016/07/20 06:00 PHST- 2016/04/08 00:00 [received] PHST- 2016/05/23 00:00 [revised] PHST- 2016/05/29 00:00 [accepted] PHST- 2016/07/20 06:00 [entrez] PHST- 2016/07/20 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/06/28 00:00 [pmc-release] AID - 10.1155/2016/9631510 [doi] PST - ppublish SO - Mediators Inflamm. 2016;2016:9631510. doi: 10.1155/2016/9631510. Epub 2016 Jun 28.