Allelic variants of the aryl hydrocarbon receptor differentially influence UVB-mediated skin inflammatory responses in SKH1 mice

• DOI: 10.1016/j.tox.2017.11.020
• Publication Date: 2017-12-05T23:21:32Z
• Authors: Kayla J. Smith; Iain A. Murray; Jacob A. Boyer; Gary H. Perdew
• Keywords: Male; 0301 basic medicine; Ultraviolet Rays; Gene Expression; Genetic Variation; Dermatitis; Mice, Transgenic; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Liver; Receptors, Aryl Hydrocarbon; Cytochrome P-450 CYP1A1; Animals; Amino Acid Sequence; Alleles; Skin

The mouse strain SKH1 is widely used in skin research due to its hairless phenotype and intact immune system. Due to the complex nature of aryl hydrocarbon receptor (AHR) function in the skin, the development of additional in vivo models is necessary to study its role in cutaneous homeostasis and pathology. Variants of the Ah allele, exist among different mouse strains. The Ahb-1 and Ahd alleles express high and low affinity ligand binding forms of the AHR, respectively. The outbred SKH1 mice express the Ahb-2 and/or Ahd alleles. SKH1 mice were crossed with C57BL/6J mice, which harbor the Ahb-1 allele, to create useful models for studying endogenous AHR function. SKH1 mice were bred to be homozygous for either the Ahb-1 or Ahd allele to establish strains for use in comparative studies of the effects of differential ligand-mediated activation through gene expression changes upon UVB exposure. Ahb-1 or Ahd allelic status was confirmed by DNA sequence analysis. We tested the hypothesis that SKH1-Ahb-1 mice would display enhanced inflammatory signaling upon UVB exposure compared to SKH1-Ahd mice. Differential basal AHR activation between the strains was determined by assessing Cyp1a1 expression levels in the small intestine, liver, and skin of the SKH1-Ahb-1 mice compared to SKH1-Ahd mice. To determine whether SKH1-Ahb-1 mice are more prone to a pro-inflammatory phenotype in response to UVB, gene expression of inflammatory mediators was analyzed. SKH1-Ahb-1 mice expressed enhanced gene expression of the chemotactic factors Cxcl5, Cxcl1, and Ccl20, as well as the inflammatory signaling factors S100a9 and Ptgs2, compared to SKH1-Ahd mice in skin. These data supports a role for AHR activation and enhanced inflammatory signaling in skin.