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Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
HIF-1alpha is essential for myeloid cell-mediated inflammation
Thorsten Cramer1, Yuji Yamanishi, Björn E Clausen
1Molecular Biology Section, Division of Biological Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|March 12, 2003
Summary
Hypoxia-inducible factor 1-alpha (HIF-1alpha) is crucial for myeloid cell function in innate immunity. Its absence impairs cell metabolism, motility, and bacterial killing during inflammation.
Area of Science:
- Immunology
- Cellular Metabolism
- Molecular Biology
Background:
- Myeloid cells, including granulocytes and macrophages, are key players in innate immunity.
- Hypoxia-inducible factor 1-alpha (HIF-1alpha) is a transcription factor activated by low oxygen conditions.
- VHL is a negative regulator of HIF-1alpha, and VEGF is a downstream target.
Purpose of the Study:
- To investigate the role of HIF-1alpha, VHL, and VEGF in myeloid cell-mediated inflammatory responses.
- To elucidate the mechanism by which HIF-1alpha regulates myeloid cell function during inflammation.
Main Methods:
- Conditional knockout mouse models for HIF-1alpha, VHL, and VEGF.
- Analysis of myeloid cell infiltration, activation, and inflammatory responses in vivo.
- Assessment of cellular ATP levels, glycolytic capacity, aggregation, motility, invasiveness, and bacterial killing.
Main Results:
- HIF-1alpha activation is essential for myeloid cell infiltration and activation, independent of VEGF.
- Loss of VHL significantly enhances acute inflammatory responses.
- Absence of HIF-1alpha drastically reduces cellular ATP by impairing glycolytic capacity in myeloid cells.
- Metabolic defects in HIF-1alpha-deficient myeloid cells lead to impaired aggregation, motility, invasiveness, and bacterial killing.
Conclusions:
- HIF-1alpha is a critical regulator of myeloid cell survival and function within the inflammatory microenvironment.
- The metabolic role of HIF-1alpha is essential for effective innate immune responses.
- Targeting HIF-1alpha may offer therapeutic strategies for modulating inflammation.
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