Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis.
OBJECTIVE
The pathogenesis of rheumatoid arthritis (RA) reflects an ongoing imbalance between proinflammatory and antiinflammatory cytokines. Interleukin-20 (IL-20) has proinflammatory properties for keratinocytes. In this study, we sought to determine whether IL-20 is involved in RA.


METHODS
We analyzed IL-20 levels in synovial fluid from RA patients. IL-20 and its receptors were detected in RA synovial fibroblasts (RASFs), using immunohistochemical staining. The effect of IL-20 on endothelial cells, neutrophils, and RASFs was investigated using MTT and migration assays. The expression of IL-20 and its receptors in healthy rats and in rats with collagen-induced arthritis (CIA) was also analyzed. Soluble IL-20 receptor type I (sIL-20RI) or sIL-20RII was administered to rats with CIA by intramuscular electroporation, and the severity of arthritis was monitored.


RESULTS
RA patients expressed significantly higher levels of synovial fluid IL-20 than did the rheumatic disease controls. IL-20 and its receptors were expressed in the synovial membranes and RASFs. IL-20 induced RASFs to secrete monocyte chemoattractant protein 1, IL-6, and IL-8, and it promoted neutrophil chemotaxis, RASF migration, and endothelial cell proliferation. Both IL-20 and IL-20RI were up-regulated in the rat CIA model. In vivo, electroporated sIL-20RI plasmid DNA decreased the severity of arthritis in the rats with CIA.


CONCLUSIONS
IL-20 was up-regulated in the synovial fluid of RA patients and acted as a chemokine that attracted the migration of neutrophils and RASFs in vitro. The rat CIA model demonstrated that IL-20 was involved in the pathogenesis of arthritis, because sIL-20RI significantly reduced arthritis in rats with CIA. Thus, IL-20 may modulate the incidence and severity of arthritis and play important roles at local sites of inflammation.
Hsu
Yu-Hsiang
YH
National Cheng Kung University, Tainan, Taiwan.
Li
Hsing-Hui
HH
Hsieh
Mei-Yi
MY
Liu
Ming-Fei
MF
Huang
Kuo-Yuan
KY
Chin
Lin-Show
LS
Chen
Pei-Chih
PC
Cheng
He-Hsiung
HH
Chang
Ming-Shi
MS
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D018929:Cell Culture Techniques; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood; D016753:Interleukin-10 / Q000097:blood*; D007378:Interleukins / Q000235:genetics; D051379:Mice; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology; D051381:Rats; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D014471:Umbilical Veins
D015415:Biomarkers; D018076:DNA, Complementary; D007378:Interleukins; D016753:Interleukin-10; C422042:interleukin 20