Elemental diet inhibits pro-inflammatory cytokine production in keratinocytes through the suppression of NF-B activation

An elemental diet (ED) has been reported to reduce oral mucositis and dermatitis induced by chemotherapy. However, its molecular mechanism of action as an anti-inflammatory agent is still unknown. The aim of the present study was to clarify whether ED confers its anti-inflammatory action via reduction of pro-inflammatory cytokine production in keratinocytes in vivo and in vitro. We evaluated the efficacy of ED in the treatment of 5-fluorouracil (5-FU)-induced dermatitis of nude mice, and examined the expression of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukin (IL)-1 and IL-6 using immunohistochemistry. Moreover, we assessed the expression and production of these pro-inflammatory cytokines by western blotting and ELISA assays, respectively, in immortalized human keratinocyte cell line, HaCaT. Furthermore, we investigated the effect of ED on a major inflammation-related factor, nuclear transcription factor-B (NF-B), since it controls many genes involved in the inflammation pathway. Our results indicated that ED reduced the expression of TNF-, IL-1 and IL-6. It also inhibited the nuclear transition of p65 NF-B, which is known to regulate inflammatory cytokine expression in keratinocytes suffering from 5-FU-induced dermatitis. In addition, ED reduced the production of TNF-, IL-1 and IL-6 in HaCaT cells. Moreover, ED attenuated 5-FU-induced transcriptional activation of NF-B. These findings revealed that ED suppresses the expression of pro-inflammatory cytokines by suppressing NF-B in keratinocytes, suggesting the potential usefulness of ED in the treatment of various inflammatory diseases of the dermal region.