HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha.
The expression of the hypoxia-responsive transcription factor hypoxia-inducible factor (HIF)-1 during acute inflammation was investigated in experimental wounds. HIF-1alpha mRNA was maximally expressed in wound cells 6 h after injury. HIF-1alpha protein was detectable in wound cells 1 and 5 days after injury. Cells from 1-day-old wounds were not hypoxic, as determined by lack of pimonidazole hydrochloride adduct formation. Tumor necrosis factor (TNF)-alpha, but not interleukin-1beta, increased the HIF-1alpha protein content of cells isolated 1 and 5 days after injury, and also of glycogen-elicited peritoneal cells, but not HIF-1alpha mRNA. HIF-1alpha did not accumulate in TNF-alpha-treated HeLa, NIH/3T3, NR8383, or RAW 264.7 cells. Nitric oxide from S-nitrosoglutathione did not induce HIF-1alpha accumulation or modulate the response to TNF-alpha. TNF-alpha did not increase oxygen consumption or result in the production of reactive oxygen intermediates by day 1 wound cells. Vascular endothelial growth factor mRNA in wound cells peaked 24 h after wounding. HIF-1 expression in early wounds may contribute to the regulation of inducible nitric oxide synthase and vascular endothelial growth factor, two HIF-1-responsive genes intimately related to the process of repair.
Albina
J E
JE
Division of Surgical Research, Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island 02903, USA. Jorge_Albina@Brown.edu
Mastrofrancesco
B
B
Vessella
J A
JA
Louis
C A
CA
Henry
W L
WL
Reichner
J S
JS
D000818:Animals; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D008297:Male; D009593:Nitroimidazoles / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000502:physiology*
D016228:Endothelial Growth Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007375:Interleukin-1; D008222:Lymphokines; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C033815:pimonidazole