학술논문
HIF1α-dependent hypoxia response in myeloid cells requires IRE1α.
Document Type
Article
Author
Mawambo, Gaëlle; Oubaha, Malika; Ichiyama, Yusuke; Blot, Guillaume; Crespo-Garcia, Sergio; Dejda, Agnieszka; Binet, François; Diaz-Marin, Roberto; Sawchyn, Christina; Sergeev, Mikhail; Juneau, Rachel; Kaufman, Randal J.; Affar, El Bachir; Mallette, Frédérick A.; Wilson, Ariel M.; Sapieha, Przemyslaw
Source
Subject
*MYELOID cells
*WARBURG Effect (Oncology)
*HYPOXIA-inducible factors
*HYPOXEMIA
*CELL physiology
*MACROPHAGES
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Language
ISSN
1742-2094
Abstract
Cellular adaptation to low oxygen tension triggers primitive pathways that ensure proper cell function. Conditions of hypoxia and low glucose are characteristic of injured tissues and hence successive waves of inflammatory cells must be suited to function under low oxygen tension and metabolic stress. While Hypoxia-Inducible Factor (HIF)-1α has been shown to be essential for the inflammatory response of myeloid cells by regulating the metabolic switch to glycolysis, less is known about how HIF1α is triggered in inflammation. Here, we demonstrate that cells of the innate immune system require activity of the inositol-requiring enzyme 1α (IRE1α/XBP1) axis in order to initiate HIF1α-dependent production of cytokines such as IL1β, IL6 and VEGF-A. Knockout of either HIF1α or IRE1α in myeloid cells ameliorates vascular phenotypes in a model of retinal pathological angiogenesis driven by sterile inflammation. Thus, pathways associated with ER stress, in partnership with HIF1α, may co-regulate immune adaptation to low oxygen. [ABSTRACT FROM AUTHOR]