title: The eicosanoid response to high dose UVR exposure of individuals prone and resistant to sunburn.
abstract: High personal UVR doses can be gained during leisure activities, causing intense self-resolving inflammation (sunburn) of unprotected skin. UVR activates release of membrane fatty acids and upregulates their metabolism by cyclooxygenases (COX) and lipoxygenases (LOX) to different eicosanoids. While COX-derived prostaglandin (PG)E(2) is a potent mediator of sunburn vasodilatation, LOX-derived 15-hydroxyeicosatetraenoic acid (HETE) and its lipoxin metabolites may contribute to sunburn limitation. We explored the relationships between expression of these lipid mediators and the clinical and histological outcomes, comparing responses of individuals prone and more resistant to sunburn. An acute UVR exposure of 12 SED (standard erythema dose) was applied to buttock skin of 32 white Caucasians (n = 16 phototype I/II, n = 16 phototype III/IV), and over the subsequent 72 h assessments were made of skin erythema, immunohistochemical expression of leukocyte markers, COX-2, 12-LOX, 15-LOX and nitric oxide synthase (NOS), and eicosanoid levels by LC/ESI-MS/MS. Evidence of a significant inflammatory response was seen earlier in phototype I/II with regard to expression of erythema (4 h, p < 0.001), neutrophil infiltration (24 h, p = 0.01), epidermal COX-2 (24 h, p < 0.05) and 12-LOX (24 h, p < 0.01), and dermal eNOS (24 h, p < 0.05) proteins, although CD3+ lymphocyte infiltration showed an earlier increase in phototype III/IV (24 h, p < 0.05). Although erythema was equivalent at 72 h in both groups, phototype I/II showed higher PGE(2) accompanied by elevated 15-HETE, and a strong positive correlation was seen between these mediators (n = 18, r = 0.805, p = 0.0001). Hence anti-inflammatory eicosanoid 15-HETE may temper the pro-inflammatory milieu in sunburn, having greater influence in those prone to sunburn than those more resistant, given the same high UVR exposure conditions.
authors.affiliation: Bradford School of Pharmacy, School of Life Sciences, University of Bradford, Richmond Road, Bradford, UK BD7 1DP. a.nicolaou@bradford.ac.uk
authors.forename: Anna
authors.initials: A
authors.lastname: Nicolaou
authors.forename: Mojgan
authors.initials: M
authors.lastname: Masoodi
authors.forename: Karl
authors.initials: K
authors.lastname: Gledhill
authors.forename: Ann Katarina
authors.initials: AK
authors.lastname: Haylett
authors.forename: Anthony John
authors.initials: AJ
authors.lastname: Thody
authors.forename: Desmond John
authors.initials: DJ
authors.lastname: Tobin
authors.forename: Lesley Elizabeth
authors.initials: LE
authors.lastname: Rhodes
mesh_terms: D000328:Adult; D017252:CD3 Complex / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D004198:Disease Susceptibility; D004307:Dose-Response Relationship, Radiation; D015777:Eicosanoids / Q000096:biosynthesis / Q000378:metabolism*; D004890:Erythema / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000528:radiation effects; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism; D012867:Skin / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D013471:Sunburn / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D017252:CD3 Complex; D002630:Chemotactic Factors; D015777:Eicosanoids; D011453:Prostaglandins; D008084:Lipoxygenase; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases