Platelet-derived growth factor-AA increases IL-1 beta and IL-8 expression and activates NF-kappa B in rheumatoid fibroblast-like synoviocytes

초록

The effect of platelet-derived growth factor (PDGF)-AA on the inflammation in rheumatoid arthritis (RA) and osteoarthritis (OA) was investigated using cultured fibroblast-like synoviocytes (FLS) obtained from RA and OA patients as well as control nonarthritic (NA) individuals. PDGF-AA increased the mRNA and protein expressions of proinflammatory cytokines, interleukin (IL)-1beta and IL-8 in RA FLS. Biological activity of IL-1 in the culture supernatant of RA FLS was also increased by PDGF-AA stimulation. Interestingly, PDGF-AA synergized with tumour necrosis factor (TNF)-alpha to upregulate the protein expressions of IL-1beta and IL-8. PDGF-induced enhancement of the IL-1beta and IL-8 mRNA expressions was also observed in OA FLS. However, the expression of these proinflammatory cytokines in NA FLS did not change by PDGF treatment, suggesting that the inflammatory condition might have modified the biological effects of PDGF. In accordance with the enhanced expression of inflammatory cytokines, the activity of nuclear factor kappaB was also induced in response to PDGF-AA in RA FLS. These results suggest that PDGF-AA plays an important role in the progression of RA inflammation, and inhibiting PDGF activity may be useful for the effective RA treatment.

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