Elemental diet inhibits pro‑inflammatory cytokine production in keratinocytes through the suppression of NF‑κB activation

Harada,Koji; Ferdous,Tarannum; Mizukami,Yoichi; Mishima,Katsuaki

doi:10.3892/or.2018.6440

Elemental diet inhibits pro‑inflammatory cytokine production in keratinocytes through the suppression of NF‑κB activation

Authors:
- Koji Harada
- Tarannum Ferdous
- Yoichi Mizukami
- Katsuaki Mishima
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Affiliations: Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Center for Gene Research, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan
Published online on: May 16, 2018 https://doi.org/10.3892/or.2018.6440
Pages: 361-368

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Abstract

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‑α (TNF‑α), interleukin (IL)‑1β 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‑κB (NF‑κB), since it controls many genes involved in the inflammation pathway. Our results indicated that ED reduced the expression of TNF‑α, IL‑1β and IL‑6. It also inhibited the nuclear transition of p65 NF‑κB, which is known to regulate inflammatory cytokine expression in keratinocytes suffering from 5‑FU‑induced dermatitis. In addition, ED reduced the production of TNF‑α, IL‑1β and IL‑6 in HaCaT cells. Moreover, ED attenuated 5‑FU‑induced transcriptional activation of NF‑κB. These findings revealed that ED suppresses the expression of pro‑inflammatory cytokines by suppressing NF‑κB in keratinocytes, suggesting the potential usefulness of ED in the treatment of various inflammatory diseases of the dermal region.

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