Induction of macrophage inflammatory protein 2 gene expression by interleukin 1β in rat lung

Abstract

Background - Recruitment of inflammatory cells in the lungs may contribute to tissue injury as a result of mediators released from these cells. Interleukin 1p (IL-1,β) is a potent inducer of neutrophil accumulation, a process that may require local protein biosynthesis. Macrophage inflammatory protein 2 (MIP-2) is a ∼ 6 kD heparin binding protein and is a member of the C-X-C superfamily that causes significant neutrophil chemotaxis and activation in vitro. A study was performed to determine whether IL-lp could induce the expression of MIP-2 in the lungs of Brown-Norway rats. Methods - rhIL-lβ (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 prepared from cDNA obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) of BAL cells obtained from a rat treated with lipopolysaccharide. 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-1β induced a significant influx of neutrophils into BAL fluid with 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 airway mononuclear cells and airway epithelium at four hours after IL-1β at 24 hours the signal had nearly gone. Conclusion - IL-1β induces the expression of MIP-2 mRNA in rat lung. MIP-2 may be one chemokine that could contribute to IL-1β induced neutrophil influx.