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

We investigated the effect of several immune-relevant cytokines on expression of the chemoattractant intercrine/chemokine RANTES in a mouse mesangial cell line (MMC). Fifty ng/ml recombinant tumor necrosis factor alpha (TNFalpha) induced a marked increase in RANTES transcripts after 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 RANTES, as assessed by indirect immunofluorescence and Western blotting, increased in MMCs 24 hours after TNFalpha stimulation. Interleukin-1beta, tumor necrosis factor beta (TNFbeta), and lipopolysaccharide (LPS) also increased expression of RANTES mRNA. In addition, RANTES mRNA expression was stimulated in glomeruli harvested from rats following renal in vivo perfusion with TNFalpha. Our results indicate that mesangial cells produce the small cytokine RANTES. This factor, in concert with other chemoattractants, may play a role in the glomerular recruitment of inflammatory cells like macrophages/monocytes.