IL-4 enhances hypoxia induced HIF-1alpha protein levels in human transformed intestinal cells.
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that mediates the adaptive response to hypoxia. Increasing evidence suggests a crucial role for HIF-1 in immune reactions. Here we investigated the effect of the Th2 type cytokines IL-4 and IL-10 on HIF-1alpha mediated response in normoxia (21% O2) and hypoxia (1% O2). Incubation of human transformed intestinal cells (HT-29) with IL-4 significantly increased HIF-1alpha protein levels during hypoxia but not during normoxia. Mechanisms involved are IL-4 induced up-regulation of HIF-1alpha gene transcription and the PI3K signaling pathway. The increase in hypoxia-induced accumulation of HIF-1alpha protein after IL-4 treatment did not result in up-regulation of HIF-1 DNA-binding activity or HIF-1 dependent gene expression. IL-10 did not affect HIF-1alpha protein levels.
Scharte
Marion
M
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Germany. scharte@anit.uni-muenster.de
Jurk
Kerstin
K
Kehrel
Beate
B
Zarbock
Alexander
A
Van Aken
Hugo
H
Singbartl
Kai
K
D015687:Cell Hypoxia / Q000187:drug effects; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508609:IL10 protein, human; C508598:IL4 protein, human; D016753:Interleukin-10; D015847:Interleukin-4; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases