OBJECTIVE

A low pH microenvironment is a characteristic feature of inflammation loci and affects the functions of immune cells. In this study, we investigated the effect of extracellular acidification on macrophage gene expression.

METHODS

RAW264.7 macrophages were incubated in neutral (pH 7.4) or acidic (pH 6.8) medium for 4 h. Global mRNA expression levels were determined using Affymetrix genechips.

RESULTS

The mRNA expressions of 353 macrophage genes were significantly modified after incubation in acidic medium; 193 were up-regulated and 160 down-regulated. Differentially regulated genes were grouped into 13 classes based on the functions of the corresponding protein products. Pathway analysis revealed that differentially expressed genes are enriched in pathways related to inflammation and immune responses. Quantitative real-time PCR analysis confirmed that the expressions of CXCL10, CXCL14, IL-18, IL-4RA, ABCA1, CCL4, IL-7R, CXCR4, TLR7, and CCL3 mRNAs were regulated by extracellular acidification.

CONCLUSIONS

The results of this study provide insights into the effects of acidic extracellular environments on macrophage gene expression.