Carcinogenesis Advance Access published online on March 26, 2007
Carcinogenesis, doi:10.1093/carcin/bgm065
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Conjugated linoleic acids (CLA) modulate UVR-induced IL-8 and PGE2 in human skin cells: potential of CLA isomers in nutritional photoprotection
1 Department of Medicine, University of Liverpool, Liverpool
2 Unilever Research Laboratories, Bedford
3 Photobiology Unit, Dermatological Sciences, University of Manchester, Manchester, UK
* Correspondence: Dr Lesley E. Rhodes, Photobiology Unit, Dermatological Sciences, University of Manchester, Salford Royal Foundation Hospital, Manchester M6 8HD, UK. Tel 44 161 206 1150, Fax 44 161 206 1156, Email lesley.e.rhodes{at}manchester.ac.uk
Conjugated linoleic acids (CLA), derivatives of linoleic acid found in food products, inhibit chemically-induced skin cancers in mice. However, their potential photoprotective properties remain unexplored. We examined whether CLA may modulate ultraviolet radiation (UVR)-induced secretion of IL-8 and PGE2, mediators implicated in UVR-induced inflammation and carcinogenesis, in human skin cells. Since TNF-
is an early mediator of UVR-effects, we also examined influence of CLA on TNF- induced mediator release. HaCaT keratinocytes were supplemented with CLA isomers cis-9-trans-11 (c9,t11-CLA; 
90%), trans-10-cis-12 (t10,c12-CLA; 90%) or all trans-trans isomers (tt-CLA; 23.7%) in tetrahydrofuran/ fetal calf serum (THF/FCS), or THF/FCS control. Supplementation of keratinocytes with c9,t11-CLA reduced UVB-induced IL-8 from 37,113 ± 2903 pg/ng protein in control cells to 14,167 ± 2063 pg/ng protein (p<0.001). Similarly, t10,c12-CLA reduced UVB-induced IL-8 to 9786 ± 1291.5 pg/ng protein (p<0.001). Additionally, t10,c12-CLA and tt-CLA inhibited TNF- induced IL-8, from 11,669 ± 1692 pg/ng protein in control cells to 5540 ± 191 (p<0.001) and 8082 ± 1298 (p<0.01) pg/ng protein, respectively. UVB-induced PGE2 release was reduced by tt-CLA supplementation, from 4.8 ± 1.2 to 1.6 ± 0.8 pg/mg protein (p<0.01), but increased by t10,c12-CLA to 8.8 ± 1 pg/mg protein (p<0.001). Influence of CLA on UVB-induced PGE2 release was further explored in CCD922SK dermal fibroblasts. CLA isomers reduced UVB-induced PGE2 in fibroblasts, reaching significance with c9,t11-CLA (98 ± 5 falling to 0 pg/mg protein, p<0.05). Hence CLA isomers differentially modulate UVB effects on skin cells in vitro. CLA-containing foods have potential in photoprotection; the cutaneous effects of individual isomers warrant clinical study.
Key Words: Conjugated Linoleic Acid • UVR • Human skin cells • Chemokine • IL-8 • PGE2 • Photoprotection
Received November 8, 2006; revised March 16, 2007; accepted March 16, 2007.