Neutrophils produce interleukin-17B in rheumatoid synovial tissue.
OBJECTIVE
T helper 17 (Th17) and mast cells produce IL-17A in RA and critically contribute to the pathogenesis of RA. However, the complete IL-17 cytokine profile in RA is unknown. The aim of the study was to systematically study the expression of IL-17 family cytokines in RA.


METHODS
The expression of all IL-17 cytokines in RA synovium and pannus as well as in the synovium of OA was determined using quantitative RT-PCR (qRT-PCR). IL-17A and IL-17B were immunostained. Peripheral blood neutrophils were analysed for IL-17B. The effect of IL-17B alone or in combination with TNF-α was tested in vitro on fibroblasts and endothelial cells.


RESULTS
In all tissues IL-17B was the most expressed IL-17 family cytokine, found in lining but most strongly expressed in human neutrophil elastase containing polymorphonuclear cells. This pattern was distinct from that of IL-17A, which was found in mast cell tryptase immunoreactive cells. Circulating neutrophils contained IL-17B, verifying the in vivo results. Fibroblasts up-regulated the expression of IL-17RB, a putative receptor of IL-17B, after TNF-α stimulation. IL-17B significantly enhanced TNF-α-induced production of G-CSF and IL-6 in fibroblasts.


CONCLUSIONS
IL-17B, which is present in synovium, may contribute to the pathogenesis of RA. IL-17B can enhance the effects of TNF-α on the production of cytokines and chemokines that control immune cell trafficking and neutrophil homeostasis in the inflamed tissues.
Biomedicum Helsinki 1, PO Box 63, University of Helsinki, FI-00014 Helsinki, Finland. jami.mandelin@helsinki.fi.
Vesa-Petteri
VP
Kouri
Juri
J
Olkkonen
Mari
M
Ainola
Tian-Fang
TF
Li
Lena
L
Björkman
Yrjö T
YT
Konttinen
Jami
J
Mandelin
D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D020381:Interleukin-17; D012313:RNA
cytokines; fibroblasts; inflammation; neutrophils; rheumatoid arthritis