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- Title
Molecular mechanisms of cis-urocanic acid and permethrin-induced alterations in cutaneous immunity.
- Authors
Prater, M. R.; Blaylock, B. L.; Holladay, S. D.
- Abstract
Cutaneous cis-urocanic acid (cUCA) or ultraviolet B exposure has been shown to cause diminished cutaneous contact hypersensitivity (CH) and to induce systemic tolerance (increased regulatory T lymphocytes) in mice. Permethrin is also a known CH inhibitor, but the molecular mechanisms are currently poorly understood. In this study, CH was evaluated in four strains of mice: an immunosensitive strain (C57BL/6N), an immunoresistant strain (SvImJ), a strain developed from C57BL/6N mice but genetically altered at both the tumor necrosis factor-alpha receptors (TNFαp55R and p75R), and a strain developed from C57BL/6N but genetically deleted at the interferon-gamma (IFNγ) locus. CH was evaluated in each group via oxazolone challenge following a 5-day exposure to intradermal (ID) cUCA or a single exposure to topical permethrin, or co-exposure to both chemicals in 5-week-old female C57BL/6N, SvImJ, and C57BL/6N mice genetically altered at the TNFα or IFNγ locus. A 5-day exposure to ID cUCA or a single exposure to topical permethrin resulted in diminished CH response in C57BL/6N mice, and this effect was exacerbated with concurrent exposure to both chemicals. CH in SvImJ was both cUCA- and permethrin-resistant relative to C57BL/6N mice, as 5-day cUCA or a single exposure to permethrin did not diminish CH, nor did concurrent exposure to cUCA and permethrin. Mice deleted at both TNFαR loci displayed similar but somewhat blunted diminished CH responses to cUCA or permethrin. This trend became significant with combined chemical exposure. IFNγ knockout mice displayed similar diminished CH responses to cUCA or permethrin alone. Unlike C57BL/6N mice, the IFNγ knockout mice did not show a further reduction in CH with combined chemical exposure. These results suggest the following:
- Subjects
CONTACT dermatitis; ACIDS; LYMPHOCYTES; ULTRAVIOLET radiation; MICE
- Publication
Photodermatology, Photoimmunology & Photomedicine, 2003, Vol 19, Issue 6, p287
- ISSN
0905-4383
- Publication type
Article
- DOI
10.1046/j.1600-0781.2003.00058.x