Differential Expression and Regulation of Macrophage Inflammatory Protein (MIP)-1α and MIP-2 Genes by Alveolar and Peritoneal Macrophages in LPS-Hyporesponsive C3H/HeJ Mice

Abstract

A point mutation in Toll-like receptor 4 (Tlr4) gene in C3H/HeJ mice underlies a defect in LPS-induced cytokine production by peritoneal macrophages (PMφ). Whether the C-C and the C-X-C chemokines are induced differently by LPS between alveolar macrophages (AMφ) and PMφ in this mice remains unclear. Thus, we examined the expression and regulation of macrophage inflammatory protein-1α (MIP-1α) and macrophage inflammatory protein-2 (MIP-2) in C3H/HeJ macrophages. These results showed that the accumulation of MIP-1α and MIP-2 mRNA increased dose dependently in response to LPS. PMφ responded to LPS to produce significantly higher levels of both chemokine mRNA and protein than AMφ. In addition, both macrophages produced much more MIP-2 than MIP-1α by the same doses of LPS stimulation. Moreover, the chemokine production by C3H/HeN macrophages was significantly higher than that of the C3H/HeJ macrophages. IFN-γ suppressed the LPS-induced MIP-1α release but enhanced the LPS-induced MIP-2 secretion in both macrophages. These results show that the chemokine production was induced and regulated differentially in AMφ and PMφ.