Mechanism of heat shock transcription factor 2 promotes inflammatory response in Crohn's disease through HMGB1-TLR4-NF-κB signaling

doi:10.12092/j.issn.1009-2501.2019.04.002

Abstract

Abstract:

AIM: To study the mechanism of heat shock transcription factor 2 (HSF2) promoting the inflammatory response of Crohn's disease in mice through HMGB1-TLR4-NF-κB signaling. METHODS: The model of Crohn's disease mice was established by 2,4,6-three nitrobenzene sulfonic acid (TNBS). Mice were divided into normal group, model group, control group and experimental group. The control group used high mobility group protein 1 (HMGB1) antibody to block the HMGB1 signal. The control group and the experimental group were treated with recombinant HSF2. To observe the general living conditions of mice (including survival, body weight, stool traits, eating and drinking state, hair glossiness, mental state and activity state), the disease activity index (DAI) of mice was used to evaluate the condition of the mice. Hematoxylin eosin (HE) staining was used to detect the pathological changes of intestinal tissue in mice. Immunohistochemical staining (IHC) was used to detect the expression of P-65 in intestinal tissue of mice. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the colon tissue of mice. Western-Blot was used to detect the expression level of HMGB1, Toll like receptor 4 (TLR4), NF-κB (p-P65) and myeloid differentiation factor (MyD88) in colonic tissue. RESULTS:TNBS induced mouse Crohn's disease successfully. The general living condition of the experimental group was poor, and the DAI score was significantly higher than that of the control group and the model group, with statistical significance (P<0.05). HE staining showed that the degree of erosion, edema and inflammatory reaction of the colon mucosa in the experimental group was higher than that in the model group and the control group. The levels of inflammatory factors IL-1β, TNF-α, IL-6 in the colon tissue of the experimental group were significantly higher than those of the model group and the control group (P<0.05). The expression level of HMGB1, TLR4, NF-κB (p-P65) and MyD88 in the tissues was significantly higher than that in the model group and the control group (P<0.05). CONCLUSION:HSF2 can promote the inflammatory response of Crohn's disease in mice by activating HMGB1-TLR4- NF-κB signaling.

Key words: heat shock transcription factor 2, Crohn's disease, inflammatory response, high mobility group box protein 1, Toll like receptor 4, NF-κB

CLC Number:

R574

RUAN Shuiliang，GUAN Qiaobing. Mechanism of heat shock transcription factor 2 promotes inflammatory response in Crohn's disease through HMGB1-TLR4-NF-κB signaling[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(4): 369-375.

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