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Heat Shock Protein 27 Regulates the Inflammatory Response of Intestinal Epithelial Cells by the Nuclear Factor-κB Pathway.
- Source :
-
Digestive diseases and sciences [Dig Dis Sci] 2020 Dec; Vol. 65 (12), pp. 3514-3520. Date of Electronic Publication: 2020 Feb 20. - Publication Year :
- 2020
-
Abstract
- Background: The specific and accurate pathogenesis of diarrhea-type irritable bowel syndrome is still unclear.<br />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.<br />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.<br />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.<br />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.
- Subjects :
- Anisoles pharmacology
Antimetabolites pharmacology
Cells, Cultured
Diarrhea
Gene Silencing
Humans
Inflammation metabolism
Irritable Bowel Syndrome physiopathology
Isoxazoles pharmacology
Phosphorylation drug effects
RNA, Small Interfering metabolism
Signal Transduction
HSP27 Heat-Shock Proteins metabolism
Intestinal Mucosa metabolism
Irritable Bowel Syndrome metabolism
NF-kappa B metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2568
- Volume :
- 65
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Digestive diseases and sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32078087
- Full Text :
- https://doi.org/10.1007/s10620-020-06074-z