Effect of sodium butyrate regulating IRAK1 (interleukin-1 receptor-associated kinase 1) on visceral hypersensitivity in irritable bowel syndrome and its mechanism

Bioengineered. 2021 Dec;12(1):1436-1444. doi: 10.1080/21655979.2021.1920324.

Abstract

The current study aimed to investigate the effects of sodium butyrate on the level of colonic protein IRAK1 (interleukin-1 receptor-associated kinase 1) in irritable bowel syndrome (IBS) models as well as revealing the relationship between IRAKI level and visceral sensitivity during the progression of IBS. IBS symptoms were induced using TNBS (2,4,6-trinitrobenzene sulfonic acid) in mice and using IL-33 in HT-29 cells, which were then hanlded with sodium butyrate (100 mM for each mice and 0.05 M for HT-29 cells). The threshold of visceral pain and the expression of IRAKI in mice, and the level of IRAKI in HT-29 cells were detected. The data showed that the level of IRAK1 in IBS mice was higher than that in the control group, while the pre-treatment with sodium butyrate could solidy suppressed the level of IRAK1. Morevoer, it was found that the level of IRAK1 was negatively correlated with the pain threshold. In in vitro assays, the level of IRAK1 was firstly induced by IL-33 stimulation and then suppressed by sodium butyrate pretreatment. Collectively, the level of IRAKI showed an obvioulty positive relation with visceral hypersensitivity in IBS models, and the treatment with sodium butyrate could alleviate visceral hypersensitivity by inhibiting the expression of IRAKI.

Keywords: IBS; IRAK1; Sodium butyrate; mechanism; visceral hypersensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyric Acid / pharmacology*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • HT29 Cells
  • Humans
  • Interleukin-1 Receptor-Associated Kinases* / genetics
  • Interleukin-1 Receptor-Associated Kinases* / metabolism
  • Irritable Bowel Syndrome* / metabolism
  • Irritable Bowel Syndrome* / pathology
  • Irritable Bowel Syndrome* / physiopathology
  • Male
  • Mice
  • Signal Transduction / drug effects
  • Visceral Pain / metabolism
  • Visceral Pain / physiopathology

Substances

  • Butyric Acid
  • IRAK1 protein, human
  • Interleukin-1 Receptor-Associated Kinases
  • Irak1 protein, mouse

Grants and funding

This work was supported by grants from the Natural Science Foundation of China [no. 81700466/H0307]. [Recipient: Yuqin He]. General Program of Chongqing Natural Science Foundation [cstc2019jcyj-msxmX0384] [Recipient: Yuqin He].