TNF-ALPHA INDUCES EXPRESSION OF THE CHEMOATTRACTANT CYTOKINE RANTES IN CULTURED MOUSE MESANGIAL CELLS

We investigated the effect of several immune-relevant cytokines on exp ression of the chemoattractant intercrine/chemokine RANTES in a mouse mesangial cell line (MMC). Fifty ng/ml recombinant tumor necrosis fact or alpha (TNFalpha) induced a marked increase in RANTES transcripts af ter two hours. RANTES mRNA remained elevated for 24 to 48 hours after stimulation, and could be abolished by co-incubation with 30 mug/ml of a neutralizing rabbit anti-TNFalpha antibody. Protein expression of R ANTES, as assessed by indirect immunofluorescence and Western blotting , increased in MMCs 24 hours after TNFalpha stimulation. Interleukin-1 beta, tumor necrosis factor beta (TNFbeta), and lipopolysaccharide (LP S) also increased expression of RANTES mRNA. In addition, RANTES mRNA expression was stimulated in glomeruli harvested from rats following r enal in vivo perfusion with TNFalpha. Our results indicate that mesang ial cells produce the small cytokine RANTES. This factor, in concert w ith other chemoattractants, may play a role in the glomerular recruitm ent of inflammatory cells like macrophages/monocytes.