INTERLEUKIN-1-ALPHA STIMULATES KC SYNTHESIS IN RAT MESANGIAL CELLS - GLUCOCORTICOIDS INHIBIT KC INDUCTION BY IL-1

To assess the possible role of the production of chemokines by intrins ic glomerular cells in the generation of inflammation in glomeruloneph ritis, the chemokine, KC, was cloned from a rat macrophage cDNA Librar y. Transfection of rat KC into COS-7 cells resulted in increased neutr ophil chemotactic activity. The KC cDNA was expressed as a fusion prot ein in Escherichia coli for generation of an antibody. By using a ribo probe derived from the cDNA and the antibody, interleukin-1 (IL-1) was found to induce the expression of KC in rat mesangial cells. The indu ction of KC by IL-1 could be inhibited by dexamethasone (DEX). The pro tein synthesis inhibitor cycloheximide reversed the DEX-mediated inhib ition, which suggested that new protein synthesis was necessary for th e inhibitory effect. A nuclear runoff analysis indicated that DEX inhi bited the transcription of KC induced by IL-1. The stability of KC mRN A was not decreased in the presence of DEX. Furthermore, immunoblots s howed that DEX also inhibited KC expression at the level of translatio n. Together the inhibition of transcription and translation of the KC gene by DEX contribute to decreased KC expression in mesangial cells. The finding that mesangial cells express KC in response to proinflamma tory cytokines, such as IL-1, points to a central role for the mesangi al cell as a chemotactic source in glomerular inflammation.