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Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing.
- Source :
-
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2014 Aug 15; Vol. 307 (4), pp. C349-57. Date of Electronic Publication: 2014 Jul 02. - Publication Year :
- 2014
-
Abstract
- Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wound healing between the LAR mice and their littermate controls was no longer present, suggesting that decreased myeloid cell ARNT function may be an important factor in impaired wound healing in diabetes. Deferoxamine (DFO) improves wound healing by increasing hypoxia-inducible factors, which require ARNT for function. DFO was not effective in wounds of LAR mice, again suggesting that myeloid cells are important for normal wound healing and for the full benefit of DFO. These findings suggest that myeloid ARNT is important for immune function and wound healing. Increasing ARNT and, more specifically, myeloid ARNT may be a therapeutic strategy to improve wound healing.<br /> (Copyright © 2014 the American Physiological Society.)
- Subjects :
- Aged
Animals
Aryl Hydrocarbon Receptor Nuclear Translocator genetics
Case-Control Studies
Cells, Cultured
Cytokines genetics
Cytokines metabolism
Deferoxamine pharmacology
Dermatitis genetics
Dermatitis immunology
Dermatitis metabolism
Dermatitis pathology
Diabetes Complications genetics
Diabetes Complications immunology
Diabetes Complications metabolism
Diabetes Complications pathology
Diabetes Mellitus, Experimental genetics
Diabetes Mellitus, Experimental immunology
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Experimental pathology
Female
Gene Expression Regulation
Genotype
Graft Survival
Humans
Inflammation Mediators metabolism
Integrases genetics
Macrophage Activation
Macrophages immunology
Macrophages metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Middle Aged
Monocytes immunology
Monocytes metabolism
Muramidase genetics
Myeloid Cells drug effects
Myeloid Cells immunology
Phenotype
RNA, Messenger metabolism
Skin immunology
Skin metabolism
Skin pathology
Skin Transplantation
Time Factors
Aryl Hydrocarbon Receptor Nuclear Translocator deficiency
Aryl Hydrocarbon Receptor Nuclear Translocator metabolism
Immunity, Innate genetics
Immunocompromised Host genetics
Myeloid Cells metabolism
Transplantation Tolerance genetics
Wound Healing drug effects
Wound Healing genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1563
- Volume :
- 307
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Cell physiology
- Publication Type :
- Academic Journal
- Accession number :
- 24990649
- Full Text :
- https://doi.org/10.1152/ajpcell.00306.2013