期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 115, 期 7, 页码 1806-1815出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI23865
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资金
- NCI NIH HHS [CA82515, R01 CA082515] Funding Source: Medline
- NIAID NIH HHS [AI48694, R01 AI048694] Funding Source: Medline
Hypoxia is a characteristic feature of the tissue microenvironment during bacterial infection. Here we report on our use of conditional gene targeting to examine the contribution of hypoxia-inducible factor 1, a subunit (HIF-1 alpha) to myeloid cell innate immune function. HIF-1 alpha was induced by bacterial infection, even under normoxia, and regulated the production of key immune effector molecules, including granule proteases, antimicrobial peptides, nitric oxide, and TNF-alpha. Mice lacking HIF-1 alpha. in their myeloid cell lineage showed decreased bactericidal activity and failed to restrict systemic spread of infection from an initial tissue focus. Conversely, activation of the HIF-1 alpha. pathway through deletion of von Hippel-Lindau tumor-suppressor protein or pharmacologic inducers supported myeloid cell production of defense factors and improved bactericidal capacity. HIF-1 alpha control of myeloid cell activity in infected tissues could represent a novel therapeutic target for enhancing host defense.
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