Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury

Hanako Kobayashi, Victoria Gilbert, Qingdu Liu, Pinelopi P. Kapitsinou, Travis L. Unger, Jennifer Rha, Stefano Rivella, Detlef Schlöndorff, Volker H. Haase*

*Corresponding author for this work

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Renal fibrosis and inflammation are associated with hypoxia, and tissue pO 2 plays a central role in modulating the progression of chronic kidney disease. Key mediators of cellular adaptation to hypoxia are hypoxia-inducible factor (HIF)-1 and -2. In the kidney, they are expressed in a cell type-specific manner; to what degree activation of each homolog modulates renal fibrogenesis and inflammation has not been established. To address this issue, we used Cre-loxP recombination to activate or to delete both Hif-1 and Hif-2 either globally or cell type specifically in myeloid cells. Global activation of Hif suppressed inflammation and fibrogenesis in mice subjected to unilateral ureteral obstruction, whereas activation of Hif in myeloid cells suppressed inflammation only. Suppression of inflammatory cell infiltration was associated with downregulation of CC chemokine receptors in renal macrophages. Conversely, global deletion or myeloid-specific inactivation of Hif promoted inflammation. Furthermore, prolonged hypoxia suppressed the expression of multiple inflammatory molecules in noninjured kidneys. Collectively, we provide experimental evidence that hypoxia and/or myeloid cell-specific HIF activation attenuates renal inflammation associated with chronic kidney injury.

Original languageEnglish (US)
Pages (from-to)5106-5115
Number of pages10
JournalJournal of Immunology
Volume188
Issue number10
DOIs
StatePublished - May 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kobayashi, H., Gilbert, V., Liu, Q., Kapitsinou, P. P., Unger, T. L., Rha, J., Rivella, S., Schlöndorff, D., & Haase, V. H. (2012). Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury. Journal of Immunology, 188(10), 5106-5115. https://doi.org/10.4049/jimmunol.1103377