RRC ID 10841
Author Shirato K, Kizaki T, Sakurai T, Ogasawara JE, Ishibashi Y, Iijima T, Okada C, Noguchi I, Imaizumi K, Taniguchi N, Ohno H.
Title Hypoxia-inducible factor-1alpha suppresses the expression of macrophage scavenger receptor 1.
Journal Pflugers Arch
Abstract Macrophages are distributed in all peripheral tissues and play a critical role in the first line of the innate immune defenses against bacterial infection by phagocytosis of bacterial pathogens through the macrophage scavenger receptor 1 (MSR1). Within tissues, the partial pressure of oxygen (pO2) decreases depending on the distance of cells from the closest O2-supplying blood vessel. However, it is not clear how the expression of MSR1 in macrophages is regulated by low pO2. On the other hand, hypoxia-inducible factor (HIF)-1alpha is well known to control hypoxic responses through regulation of hypoxia-inducible genes. Therefore, we investigated the effects of hypoxia and HIF-1alpha on MSR1 expression and function in the macrophage cell line RAW264. Exposure to 1% O2 or treatment with the hypoxia-mimetic agent cobalt chloride (CoCl2) significantly suppressed the expression of MSR1 mRNA, accompanied by a markedly increase in levels of nuclear HIF-1alpha protein. The overexpression of HIF-1alpha in RAW264 cells suppressed the expression of MSR1 mRNA and protein, transcriptional activity of the MSR1 gene, and phagocytic capacity against the Gram-positive bacteria Listeria monocytogenes. The suppression of MSR1 mRNA by hypoxia or CoCl2 was inhibited by YC-1, an inhibitor of HIF-1alpha, or by the depletion of HIF-1alpha expression by small interference RNA. These results indicate that hypoxia transcriptionally suppresses MSR1 expression through HIF-1alpha.
Volume 459(1)
Pages 93-103
Published 2009-11-1
DOI 10.1007/s00424-009-0702-y
PMID 19641936
MeSH Animals Antimutagenic Agents / pharmacology Blotting, Western Cell Hypoxia / physiology* Cell Line Cobalt / pharmacology Gene Expression Gene Expression Regulation* Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Macrophages / metabolism* Male Mice Mice, Inbred BALB C Oxygen Partial Pressure RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction Scavenger Receptors, Class A / biosynthesis* Transfection
IF 3.158
Times Cited 25
DNA material MSR1 promoter-Luc (RDB08522)
Human and Animal Cells RAW 264 (RCB0535)