Carcinogenesis Advance Access first published online on March 8, 2006
This version published online on March 23, 2006
Carcinogenesis, doi:10.1093/carcin/bgl006
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1 Institute of BioAgricultural Sciences, Academia Sinica, Taipei 115, Taiwan, ROC
* To whom correspondence should be addressed. 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 the present study, we evaluated the protective effects of CA against UVB radiation-induced IL-10 expression and phosphorylation of mitogen-activated protein kinases 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 (ERK), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38), and the downstream transcription factors activator protein-1 (AP-1) and nuclear factor kappa B (NF-
Received October 13, 2005
Revised February 20, 2006
Accepted March 3, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Caffeic acid suppresses UVB radiation-induced expression of interleukin-10 and activation of mitogen-activated protein kinases in mouse
Vanisree Staniforth 1,
Lu-Tang Chiu 1,
and
Ning-Sun Yang 1 *
Ning-Sun Yang, E-mail: nsyang{at}gate.sinica.edu.tw
Abstract 
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.
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