IL-32 and IL-17 interact and have the potential to aggravate osteoclastogenesis in rheumatoid arthritisReport as inadecuate




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Arthritis Research and Therapy

, 14:R246

First Online: 13 November 2012Received: 20 June 2012Revised: 30 July 2012Accepted: 25 October 2012

Abstract

IntroductionInterleukin IL-32 and IL-17 play critical roles in pro-inflammatory responses and are highly expressed in the synovium of patients with rheumatoid arthritis RA. We investigated the relations between these two cytokines IL-17 and IL-32 for their ability to induce each other and to stimulate osteoclasts in RA fibroblast-like synoviocytes FLSs and T cells.

MethodsFLSs were isolated through surgical synovectomy obtained from patients with RA or osteoarthritis OA. Real-time PCR were performed to evaluate the expression of IL-32, IL-17 and osteoclast-related genes. Immunohistochemical staining and tartrate-resistant acid phosphatase TRAP staining were performed to determine the distribution of inflammatory cytokines and the presence of osteoclastogenesis.

ResultsIL-17 induced the expression of IL-32 in the FLSs from RA patients, as assessed by microarray. IL-32 production was increased by IL-17. IL-32 in the FLSs from RA patients induced the production of IL-17 in CD4 T cells. IL-32 and IL-17 were colocalized near TRAP-positive areas in joint specimens. IL-17 and IL-32 synergistically induced the differentiation of osteoclasts, as demonstrated by the expression of osteoclast-related genes. IL-32 and IL-17 also could induce resorption by osteoclasts in a RANKL-dependent manner.

ConclusionsIL-17 affected the expression of IL-32 in FLSs of RA patients and IL-32 induced the production of IL-17 in CD4+ T cells. Both IL-17 and IL-32 cytokines can reciprocally influence each other-s production and amplify the function of osteoclastogenesis in the in RA synovium. Separately, IL-17 and IL-32 each stimulated osteoclastogenesis without RANKL. Together, the two cytokines synergistically amplified the differentiation of osteoclasts, independent of RANKL stimulation.

AbbreviationsANOVAanalysis of variance

CIAcollagen-induced arthritis

CIItype II collagen

Cpcrossing point

DCdendritic cell

FBSfetal bovine serum

ELISAenzyme-linked immunosorbent assay

FACSfluorescence-activated cell sorter

FLSfibroblast-like synoviocyte

HandEhematoxylin and eosin

IFNinterferon

ILinterleukin

M-CSFmacrophage colony-stimulating factor

MMPmatrix metalloproteinase

MNCmultinucleated cell

NF-κBnuclear factor-κB

NKnatural killer

OAosteoarthritis

PI3Kphosphatidylinositol PI-3 kinase

PBMCperipheral blood mononuclear cell

PCRpolymerase chain reaction

RArheumatoid arthritis

RANKLreceptor activator of nuclear factor kappa-B ligand

RBCred blood cell

SDFstromal cell-derived factor

TCRT cell receptor

ThT helper

TLRtoll-like receptor

TNFtumor necrosis factor

TRAPtartrate-resistant acid phosphatase.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4089 contains supplementary material, which is available to authorized users.

Young-Mee Moon, Bo-Young Yoon contributed equally to this work.

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Author: Young-Mee Moon - Bo-Young Yoon - Yang-Mi Her - Hye-Joa Oh - Jae-Seon Lee - Kyoung-Woon Kim - Seon-Yeong Lee - Yun-Ju Woo -

Source: https://link.springer.com/







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