Identification of macrophage genes responsive to extracellular acidification
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Inflammation Research
ORIGINAL RESEARCH PAPER
Identification of macrophage genes responsive to extracellular acidification Seung-Yoon Park • In-San Kim
Received: 18 September 2012 / Revised: 6 December 2012 / Accepted: 2 January 2013 / Published online: 16 February 2013 Ó Springer Basel 2013
Abstract 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
Responsible Editor: Graham Wallace.
Electronic supplementary material The online version of this article (doi:10.1007/s00011-013-0591-6) contains supplementary material, which is available to authorized users. S.-Y. Park Department of Biochemistry, School of Medicine, Medical Institute of Dongguk University, Dongguk University, Gyeongju 780-714, Republic of Korea I.-S. Kim (&) Department of Biochemistry and Cell Biology, School of Medicine, Cell and Matrix Research Institute, Kyungpook National University, 101 Dongin-dong, Jung-gu, Daegu 700-422, Republic of Korea e-mail: [email protected] I.-S. Kim Biomedical Research Institute, Korea Institute Science and Technology, Seoul, Republic of Korea
inflammation and immune responses. Quantitative realtime PCR analysis confirmed that the expressions of CXCL10, CXCL14, IL-18, IL-4RA, ABCA1, CCL4, IL7R, CXCR4, TLR7, and CCL3 mRNAs were regulated by extracellular acidification. Conclusion The results of this study provide insights into the effects of acidic extracellular environments on macrophage gene expression. Keywords Gene expression Extracellular acidification Macrophages Microarray
Introduction A low pH environment is a common feature of physiological and pathological conditions associated with acute or chronic inflammation. Acidification in the inflammatory regions (pH 5.5–7.0) results from the production of shortchain fatty acids via bacterial metabolism, local lactate production by infiltrating neutrophils and macrophages, and hypoxia at the inflammatory locus [1–5]. For example, the extracellular pH of synovial fluid in rheumatoid arthritis ranges from 6.7 to 7.4 [6], and in solid tumors extracellular pH values range from 5.8 to 7.6 [7, 8]. Inflammation in healthy individuals is self-limited and resolved by a multiple step active termination program involving the blockade of neutrophil recruitment by phagocyte-derived signals and apoptotic loss of inflammatory neutrophils and their subs
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