Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia - PubMed (original) (raw)
. 2009 Feb;10(2):195-202.
doi: 10.1038/ni.1683. Epub 2009 Jan 4.
Affiliations
- PMID: 19122655
- DOI: 10.1038/ni.1683
Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia
Peter Rosenberger et al. Nat Immunol. 2009 Feb.
Erratum in
- Corrigendum: Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia.
Rosenberger P, Schwab JM, Mirakaj V, Masekowsky E, Mager A, Morote-Garcia JC, Unertl K, Eltzschig HK. Rosenberger P, et al. Nat Immunol. 2015 May;16(5):544. doi: 10.1038/ni0515-544a. Nat Immunol. 2015. PMID: 25898201 No abstract available.
Abstract
The neuronal guidance molecule netrin-1 is linked to the coordination of inflammatory responses. Given that mucosal surfaces are particularly prone to hypoxia-elicited inflammation, we sought to determine the function of netrin-1 in hypoxia-induced inflammation. We detected hypoxia-inducible factor 1alpha (HIF-1alpha)-dependent induction of expression of the gene encoding netrin-1 (Ntn1) in hypoxic epithelia. Neutrophil transepithelial migration studies showed that by engaging A2B adenosine receptor (A2BAR) on neutrophils, netrin-1 attenuated neutrophil transmigration. Exogenous netrin-1 suppressed hypoxia-elicited inflammation in wild-type but not in A2BAR-deficient mice, and inflammatory hypoxia was enhanced in Ntn1(+/-) mice relative to that in Ntn1(+/+) mice. Our studies demonstrate that HIF-1alpha-dependent induction of netrin-1 attenuates hypoxia-elicited inflammation at mucosal surfaces.
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