Interleukin-32gamma enhances the production of IL-6 and IL-8 in fibroblast-like synoviocytes via Erk1/2 activation.
BACKGROUND
In the present study, we examined the effect of the pro-inflammatory cytokine IL-32gamma, the most biologically active isoform, and its related molecules in fibroblast-like synoviocytes (FLS).


METHODS
FLS were isolated from synovial tissues of rheumatoid arthritis (RA) patients. The secretion and expression of IL-6 and IL-8 were examined by ELISA and real-time PCR, and the activation of signaling molecules was evaluated by Western blot, electrophoretic mobility shift assay (EMSA), real-time PCR, and siRNA transfection.


RESULTS
By IL-32gamma stimulation in RA FLS, the expressions of IL-6 and IL-8 were increased significantly, and the phosphorylated Erk1/2 and AP-1 were expressed prominently in Western blot and EMSA. In the Erk1/2 inhibited cells, IL-32gamma stimulation did not increase the mRNA expression of IL-6 and IL-8.


CONCLUSIONS
Our results suggest that IL-32gamma stimulation can induce the production of IL-6 and IL-8 from RA FLS via Erk1/2 activation.
Kim
Yong-Gil
YG
Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Lee
Chang-Keun
CK
Kim
Soo-Hyun
SH
Cho
Woo-Shin
WS
Mun
Se Hwan
SH
Yoo
Bin
B
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
C506536:IL33 protein, human; D000067596:Interleukin-33; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D048052:Mitogen-Activated Protein Kinase 3