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Review
. 2005 Jul;115(7):1702-4.
doi: 10.1172/JCI25740.

HIF-1alpha: a master regulator of innate host defenses?

Kol A Zarember  1 , Harry L Malech
Affiliations
Review

HIF-1alpha: a master regulator of innate host defenses?

Kol A Zarember et al. J Clin Invest. 2005 Jul.

Abstract

In the days following infection, when the human body develops and refines antibodies and prepares to mount an adaptive immune response, the bulwark of innate host defense against microbial infection is the polymorphonuclear leukocyte (PMN). PMNs seek out, identify, engulf, and sterilize invading microbes using both O2-dependent and O2-independent antimicrobial systems. A decrease in PMN numbers or function caused by immunosuppression or disease increases the risk of infection. In this issue of the JCI, Peyssonnaux et al. identify a novel and essential role for hypoxia-inducible factor-1alpha in regulating several important PMN functions relevant to host defense, including transcription of cationic antimicrobial polypeptides and induction of NO synthase.

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Figures

Figure 1
Figure 1
HIF-1α regulates several important PMN functions relevant to host defense during both normoxia and hypoxia. (A) During normoxia, O2-dependent proline hydroxylases modify HIF-1α proline residues 402 and 564. Asparagine 803 is hydroxylated by FIH, which decreases HIF-1α interaction with the p300/CBP transcriptional coactivators. The hydroxylated prolines are recognized by vHL, a component of a ubiquitin ligase complex that ubiquitinates (Ub) HIF-1α and thereby targets it for proteosomal degradation. (B) During hypoxia and/or bacterial infection, when proline hydroxylases are not active, HIF-1α regulates transcription at HREs by accumulating and binding to HIF-1β and p300/CBP, which results in transcription of hypoxia-inducible genes involved in angiogenesis, glucose transport and metabolism, erythropoiesis, inflammation, apoptosis, and cellular stress. EPO, erythropoietin.
See this image and copyright information in PMC

Comment on

References

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