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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, RESULTS. Meshes: Cell Survival, Cells, Cultured, Cytokines, Gene Expression Regulation, Humans, Keratinocytes, L-Lactate Dehydrogenase, Mitogen-Activated Protein Kinase Kinases, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Trypsin Inhibitor, Kunitz Soybean, Tumor Necrosis Factor-alpha, Ultraviolet Rays.
user
Does a soybean Kunitz trypsin inhibitor reduce tumor necrosis factor-alpha production in ultraviolet-exposed primary human keratinocytes? Context: 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-alpha (TNF-alpha) in tumor cells and inflammatory cells. The effect of KTI on TNF-alpha production in UV-exposed primary human keratinocytes was analyzed. We show (i) UV induced up-regulation of TNF-alpha mRNA and protein expression in keratinocytes; (ii) cells treated with KTI before UV irradiation showed a significantly lower accumulation of TNF-alpha protein in a dose-dependent manner and a reduced UV-induced up-regulation of TNF-alpha mRNA expression; (iii) KTI inhibited the induction of TNF-alpha target molecules interleukin-1beta (IL-1beta) 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-alpha expression; and (vii) KTI did not enhance suppression of UV-induced JNK phosphorylation by SP600125.
assistant
KTI specifically inhibited UV-induced up-regulation of cytokine expression predominantly through suppression of JNK signaling pathway. Final Decision: yes