Expression of the cytokine RANTES in human rheumatoid synovial fibroblasts. Differential regulation of RANTES and interleukin-8 genes by inflammatory cytokines.

摘要: A chronic inflammatory disease may be characterized by an accumulation of activated leukocytes at the site inflammation. Since chemokine RANTES play active role in recruiting into sites, we investigated ability cultured human synovial fibroblasts isolated from patients suffering rheumatoid arthritis to produce this and compared its regulation that closely related gene, interleukin-8 (IL-8). In unstimulated fibroblasts, expression mRNA for both chemokines was undetectable, but increased a time- dose-dependent manner upon stimulation with monokines tumor necrosis factor alpha (TNF alpha) interleukin-1 beta (IL-1 beta). Preincubation cells cycloheximide "superinduced" level IL-8 stimulated TNF IL-1 beta, decreased response alpha. addition, differential these genes noted when were combination cytokines. IL-4 down-regulated IFN gamma enhanced alpha- beta-induced increase mRNA, whereas induction or inhibited augmented IL-4. Moreover, synergistically induced expression, under same conditions, less than alone. These observations also reflected secretion. studies demonstrate expressing IL-8, participate ongoing process arthritis. observation are differentially regulated, depending presence different cytokines, indicates type cellular infiltrate progress is likely depend on relative levels stimulatory inhibitory