Department of Pharmacology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Macrophi Inc., 2217-6 Hayashi-cho, Takamatsu-shi, Kagawa-ken, 761-0301, Japan.
Biochem Biophys Res Commun. 2022 Jan 1;586:100-106. doi: 10.1016/j.bbrc.2021.11.045. Epub 2021 Nov 18.
Lipopolysaccharide (LPS) is the principal component of the outer membrane of gram-negative bacteria. The prior oral administration of LPS attenuates inflammatory responses, such as intestinal injury and atopic dermatitis, in mouse models; however, the underlying mechanism remains unclear. Here, we examined the effect of topical LPS application on allergic contact dermatitis and its mechanism of action using a murine contact hypersensitivity (CHS) model. Prolonged LPS application to the skin significantly suppressed 2,4-dinitrofluorobenzene (DNFB)-induced CHS. LPS application to the skin also reduced the phagocytosis of fluorescein isothiocyanate (FITC)-dextran by Langerhans and dendritic cells. Cutaneous cell migration into the skin-draining lymph nodes (LNs) induced by FITC painting was reduced by LPS application. During the CHS response, DNFB application induced T-cell proliferation and inflammatory cytokine production in skin-draining LNs, whereas prolonged LPS application inhibited DNFB-induced T-cell growth and interferon gamma production, indicating suppression of DNFB-induced sensitization. These results suggest that prolonged LPS application suppressed DNFB-induced sensitization and subsequently CHS response. Our findings imply that topical application of LPS may prevent allergic dermatitis such as CHS.
脂多糖(LPS)是革兰氏阴性菌外膜的主要成分。在小鼠模型中,预先口服 LPS 可减轻炎症反应,如肠道损伤和特应性皮炎;然而,其潜在机制尚不清楚。在这里,我们使用小鼠接触超敏反应(CHS)模型研究了 LPS 局部应用对过敏性接触性皮炎及其作用机制的影响。长时间 LPS 应用于皮肤可显著抑制 2,4-二硝基氟苯(DNFB)诱导的 CHS。LPS 应用于皮肤还减少了郎格汉斯和树突状细胞对异硫氰酸荧光素(FITC)右旋糖酐的吞噬作用。用 FITC 绘画诱导的皮肤引流淋巴结(LNs)中的皮肤细胞迁移减少。在 CHS 反应中,DNFB 应用于皮肤可诱导引流 LNs 中的 T 细胞增殖和炎症细胞因子产生,而长时间 LPS 应用可抑制 DNFB 诱导的 T 细胞生长和干扰素γ产生,表明抑制了 DNFB 诱导的致敏作用。这些结果表明,长时间 LPS 应用抑制了 DNFB 诱导的致敏作用,随后抑制了 CHS 反应。我们的研究结果表明,LPS 的局部应用可能预防过敏性皮炎,如 CHS。