Premium
Enhanced generation of platelet‐activating factor‐receptor ligands via ethanol synergizes ultraviolet B mediated acute and systemic effects
Author(s) -
Sahu Ravi P,
Weyerbacher Jonathan,
Ocana Jesus,
Konger Raymond,
Travers Jeffrey
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1177.20
Subject(s) - platelet activating factor , chemistry , pharmacology , hacat , ethanol , receptor , immunology , medicine , biochemistry , in vitro
Alcohol (ethanol) intoxication remains one of the most abused substance in the United States and other part of the world. In addition, an association between alcoholism and trauma has long been recognized. Moreover, thermal injury after alcohol exposure have been shown to exhibit higher morbidity and mortality in humans. However, the mechanism of alcohol‐related toxicity with or without thermal injury is not entirely clear. Several studies including ours have shown that exposure to pro‐oxidative stressors including ultraviolet B (UVB) generate the potent lipid mediator with platelet‐activating factor‐receptor (PAF‐R) ligand activity. Notably, these PAF‐R ligands mediate UVB‐induced acute pro‐inflammatory effects and also augment photosensitivity associated with the deficiency of xeroderma pigmentosum complementation group A. Given that several agents can modulate PAF‐R ligands production and systemic ethanol exposure enhances UVB‐induced effects, we hypothesize that ethanol can synergistically potentiate UVB‐mediated PAF‐R ligands production as well as acute pro‐inflammatory and systemic effects. Using the human keratinocyte‐derived cell line, HaCaT, we demonstrate that preincubation with ethanol resulted in an augmentation of PAF‐R ligands production in response to low (sub‐erythematic) doses of UVB. Pre‐treatment of C57BL/6 mice with systemic ethanol resulted in an augmented skin production of PAF‐R ligands in response to UVB. We demonstrate that pre‐treatment with systemic ethanol followed by UVB irradiation of PAF‐R positive wild‐type versus PAF‐R‐deficient mice resulted in enhanced skin erythema response compared to UVB alone treated group in a PAF‐R dependent fashion. Moreover, the combination of ethanol + UVB resulted in increased systemic toxicity, including lung inflammation only in wild‐type mice and not in the PAF‐R‐deficient mice. These studies demonstrate the involvement of the PAF‐R pathway in ethanol‐induced acute toxic effects and that ethanol can synergistically potentiate PAF‐R‐mediated systemic effects when combined with agents (such as UVB) exhibiting pro‐oxidative stressors property. These studies indicate that blocking PAF‐R‐mediated pathway could be used as a promising approach to prevent ethanol ± UVB‐mediated acute and systemic toxicities. Support or Funding Information NIH grant R01 HL062996 and K22 ES023850