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Inhibition of KDM4A Activity as a Strategy to Suppress interleukin-6 Production and Attenuate Colitis Induction

Inhibition of KDM4A Activity as a Strategy to Suppress interleukin-6 Production and Attenuate Colitis Induction

Kazuhiro Ishiguro, Osamu Watanabe, Masanao Nakamura, Takeshi Yamamura, Masanobu Matsushita, Hidemi Goto, Yoshiki Hirooka

Clin Immunol. 2017 Jul;180:120-127.

PMID: 28511912

Abstract:

4-Chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) functions as a hapten and fluoresces upon binding to proteins. Therefore, fluorescence visualization of hapten-proteins is a feature of the colitis induced by NBD-Cl. Using this colitis model, we located activated fibroblasts in the vicinity of hapten-proteins upon colitis induction and observed interleukin (IL)-6 production in the activated fibroblasts. We screened herbal ingredients using primary fibroblasts stimulated with tumor necrosis factor α (TNF-α) and found the suppressive action of Atractylodin on IL-6 production. Under TNF-α stimulation, Atractylodin induced the tri-methylation of histone H3 at lysine residue 9, which impaired the binding between NF-κB and the IL-6 promoter on the genomic DNA. Atractylodin inhibited KDM4A but not KDM6A activity. Atractylodin administration attenuated colitis induction. The KDM4A inhibitor ML324 showed similar actions on IL-6 production and colitis induction. We propose the inhibition of KDM4A activity as a strategy to suppress IL-6 production and attenuate colitis induction.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1222800794	ML324		1222800-79-4	Price

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