ISSN:
1600-0625
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background: Cytokines are produced as a consequence of photo-damaged DNA and oxidative stress in ultraviolet (UV)-exposed keratinocytes. A soybean Kunitz trypsin inhibitor (KTI) down-regulates the expression of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) in tumor cells and inflammatory cells.Aim: The effect of KTI on TNF-α production in UV-exposed primary human keratinocytes was analyzed.Results: We show (i) UV induced up-regulation of TNF-α mRNA and protein expression in keratinocytes; (ii) cells treated with KTI before UV irradiation showed a significantly lower accumulation of TNF-α protein in a dose-dependent manner and a reduced UV-induced up-regulation of TNF-α mRNA expression; (iii) KTI inhibited the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins; (iv) UV irradiation transiently activated c-Jun N-terminal kinase (JNK) and Akt signaling but only weakly activated extracellular signal-regulated kinase (ERK) and p38; (v) KTI specifically inhibited UV-induced activation of ERK, JNK, and p38, but not Akt; (vi) treatment of cells with SP600125, a pharmacological inhibitor of JNK, predominantly suppressed UV-induced up-regulation of TNF-α expression; and (vii) KTI did not enhance suppression of UV-induced JNK phosphorylation by SP600125.Conclusions: KTI specifically inhibited UV-induced up-regulation of cytokine expression predominantly through suppression of JNK signaling pathway.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1600-0625.2005.00359.x