| 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
|
|
WOS Category
|
PHYSIOLOGY
|
| Resource |
| DNA material |
MSR1 promoter-Luc (RDB08522) |
| Human and Animal Cells |
RAW 264 (RCB0535) |
