Caffeic acid suppresses UVB radiation-induced expression of interleukin10 and activation of mitogen-activated protein kinases

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 anti-cancer activities. In this study, we evaluated the protective effects of CA against UVB radiation-induced IL-10 expres-sion and phosphorylation of MAPKs in mouse skin. An in vivo transgenic IL-10 promoter–luciferase-reporter gene based assay revealed that CA inhibits the transcrip-tional 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 photocarcino-genesis 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