title: Caffeic acid suppresses UVB radiation-induced expression of interleukin-10 and activation of mitogen-activated protein kinases in mouse.
abstract: Ultraviolet B (UVB) radiation present in sunlight causes sustained immune suppression, photocarcinogenesis and photoaging in humans. Interleukin-10 (IL-10) plays a critical role in UVB-induced immune suppression by inhibiting cell-mediated immune reactions. Mitogen-activated protein kinases (MAPKs) have been implicated in UVB-induced skin carcinogenesis. Caffeic acid (CA), a phenolic acid present in many dietary plants has been shown to confer antioxidant, anti-inflammatory and anticancer activities. In this study, we evaluated the protective effects of CA against UVB radiation-induced IL-10 expression and phosphorylation of MAPKs in mouse skin. An in vivo transgenic IL-10 promoter-luciferase-reporter gene based assay revealed that CA inhibits the transcriptional activation of UVB-induced IL-10 promoter. This was further confirmed by significant inhibition of UVB radiation-induced IL-10 mRNA expression and protein production by CA in mouse skin. Contact hypersensitivity assay showed that CA could attenuate the local immune suppression induced by UVB radiation against a hapten, dinitrofluorobenzene. Our results indicated that CA might inhibit IL-10 production by interfering with an early step, prostaglandin E2 synthesis, in the activation of UVB-induced immune suppressive cytokine cascade. CA also significantly inhibited the UVB-induced activation of MAPK signal transduction pathways, such as extracellular signal-regulated protein kinase, c-Jun N-terminal protein kinase and p38 mitogen-activated protein kinase, and the downstream transcription factors activator protein-1 and nuclear factor-kappa B. The findings of our study suggest that CA may confer significant protection against UVB-induced immune suppression and photocarcinogenesis in vivo and provide the possible underlying molecular basis for its actions. Therefore, CA may have therapeutic potential as a topical protective agent against the deleterious effects of UVB radiation.
authors.affiliation: Institute of BioAgricultural Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China.
authors.forename: Vanisree
authors.initials: V
authors.lastname: Staniforth
authors.forename: Lu-Tang
authors.initials: LT
authors.lastname: Chiu
authors.forename: Ning-Sun
authors.initials: NS
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002109:Caffeic Acids; D016753:Interleukin-10; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C040048:caffeic acid