INDUCTION OF MACROPHAGE INFLAMMATORY PROTEIN-2 GENE-EXPRESSION BY INTERLEUKIN-1-BETA IN RAT LUNG

Background - Recruitment of inflammatory cells in the lungs may contri bute to tissue injury as a result of mediators released from these cel ls. Interleukin 1 beta (IL-1 beta) is a potent;inducer of neutrophil a ccumulation, a process that may require local protein biosynthesis. Ma crophage inflammatory protein 2 (MIP-2) is a similar to 6 kD heparin b inding protein and is a member of the C-X-C superfamily that causes si gnificant neutrophil chemotaxis and activation in vitro. A study was p erformed to determine whether IL-1 beta could induce the expression of MIP-2 in the lungs of Brown-Norway rats. Methods - rhIL-1 beta (500 U ) or 0.9% NaCl was injected intratracheally and bronchoalveolar lavage (BAL) cells and lung tissues were evaluated for MIP-2 mRNA expression after RNA extraction by Northern blot analysis. MIP-2 probe was prepa red from cDNA obtained by reverse transcriptase-polymerase chain react ion (RT-PCR) of BAL cells obtained from a rat treated with lipopolysac charide. Results - There was no detectable MIP-2 mRNA in the lungs of control rats but a marked enhancement of the expression at four hours with no expression at 12 hours and a slight expression at 24 hours. IL -1 beta induced a significant influx of neutrophils into BAL fluid wit h a transient increase in macrophages, In situ hybridisation of lungs using MIP-2 cDNA probe labelled with digoxigenin showed expression of MIP-2 mRNA in ah-way mononuclear cells and airway epithelium at four h ours after IL-1 beta; at 24 hours the signal had nearly gone. Conclusi on - IL-1 beta induces the expression of MIP-2 mRNA in rat lung. MIP-2 may be one chemokine that could contribute to IL-1 beta induced neutr ophil influx.