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Heat Shock Protein 27 Regulates the Inflammatory Response of Intestinal Epithelial Cells by the Nuclear Factor-κB Pathway

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Abstract

Background

The specific and accurate pathogenesis of diarrhea-type irritable bowel syndrome is still unclear.

Aims

We explored the mechanism of heat shock protein 27 (HSP27) in diarrhea-type irritable bowel syndrome to identify the key targets for the disease.

Methods

The human colonic epithelial cell lines Caco-2 and NCM460 were pretreated with KRIBB3 (a phosphorylation inhibitor of HSP27) and then stimulated with lipopolysaccharide for different times. The apoptosis ratios of Caco-2 and NCM460 cells were examined with Annexin V/PI assays. Cell growth was determined using the cell counting kit-8 assay, and the expression levels of IL-1β and IL-6 in the cell supernatant were analyzed by ELISA. In addition, the expression levels of HSP27 and the nuclear factor-κB (NF-κB) signaling pathway were examined by Western blot assay.

Results

Stimulation with lipopolysaccharide promoted the expression of HSP27 in colonic epithelial cells. HSP27 was phosphorylated at serine 78 and 82 after exposure to LPS. Apoptosis, growth inhibition, and inflammatory factor expression of lipopolysaccharide-induced colonic epithelial cells were greatly exacerbated by KRIBB3 treatment. In addition, KRIBB3 inhibited the phosphorylation of IκB-α and the activation of NF-κB. Gene silencing by small interfering RNA indicated that phosphorylation of HSP27 may regulate the NF-κB pathway.

Conclusions

HSP27 plays an important role in the inflammatory response of intestinal human colonic epithelial cells. HSP27 may protect intestinal epithelial cells against damage by regulating the NF-κB pathway.

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Funding

This study was funded by the General Program of the National Natural Science Foundation of China (Grant No. 8167032057).

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Authors and Affiliations

  1. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, Guangdong Province, China

    Yajun Zhang & Lihong Cui

  2. Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China

    Yajun Zhang, Xiaohui Wang, Shaoxin Wang, Zhihui Yan, Chao Li, Yan Zheng & Lihong Cui

Authors
  1. Yajun Zhang
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  2. Xiaohui Wang
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  3. Shaoxin Wang
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  4. Zhihui Yan
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  5. Chao Li
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  6. Yan Zheng
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  7. Lihong Cui
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Contributions

LHC and YJZ conceived and designed the experiments; YJZ, CL, and YZ performed the experiments; XHW, YJZ, and ZHY analyzed the data; LHC and YJZ wrote the paper; LHC, SXW, and YJZ revised the manuscript. All authors have reviewed and approved the final manuscript to be submitted for publication.

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Correspondence to Lihong Cui.

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The authors declare that they have no conflicts of interest.

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Zhang, Y., Wang, X., Wang, S. et al. Heat Shock Protein 27 Regulates the Inflammatory Response of Intestinal Epithelial Cells by the Nuclear Factor-κB Pathway. Dig Dis Sci 65, 3514–3520 (2020). https://doi.org/10.1007/s10620-020-06074-z

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  • DOI: https://doi.org/10.1007/s10620-020-06074-z

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