Luteolin alleviates ulcerative colitis through SHP-1/STAT3 pathway

Background Previous studies have demonstrated that Luteolin has a positive effect on epithelial barrier integrity by promoting the function of tight protein, however, little is known about the underline mechanism of Luteolin. In this study, we constructed Caco-2 cell monolayer to explore the effects...

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Bibliographic Details
Published in:Inflammation research 2021-06, Vol.70 (6), p.705-717
Main Authors: Li, Bo-Lin, Zhao, Dan-Yang, Du, Peng-Li, Wang, Xiao-Tian, Yang, Qian, Cai, Yan-Ru
Format: Article
Language:English
Subjects:
Allergology
Animals
Bile
Biomedical and Life Sciences
Biomedicine
Caco-2 Cells
Cell Membrane Permeability - drug effects
Cell viability
Colitis, Ulcerative - chemically induced
Colitis, Ulcerative - drug therapy
Colitis, Ulcerative - metabolism
Colitis, Ulcerative - pathology
Colon - drug effects
Colon - metabolism
Colon - pathology
Dermatology
Dextran
Dextran Sulfate
Dextrans
Electrical resistivity
Humans
Immunology
Inflammatory bowel disease
Integrity
Interferon
Intestine
Luteolin - pharmacology
Luteolin - therapeutic use
Male
Mice
Mice, Inbred C57BL
Monolayers
Neurology
Original Research Paper
Pharmacology/Toxicology
Phosphorylation
Phosphoserine
Phosphoserine phosphatase
Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism
Proteins
Rheumatology
SHP-1 protein
Signal transduction
Signal Transduction - drug effects
Stat3 protein
STAT3 Transcription Factor - metabolism
Tight Junction Proteins - genetics
Tight Junction Proteins - metabolism
Transcription
Tumor necrosis factor-α
Ulcerative colitis
γ-Interferon
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Summary:Background Previous studies have demonstrated that Luteolin has a positive effect on epithelial barrier integrity by promoting the function of tight protein, however, little is known about the underline mechanism of Luteolin. In this study, we constructed Caco-2 cell monolayer to explore the effects and the regulation mechanism of Luteolin in intestinal epithelial barrier integrity. Methods Caco-2 cells were co-treated with TNF-α, Interferon-γ (IFN-γ) and Luteolin for 24 h. Overexpression or knockdown of SHP-1 was applied to study the effects of protein phosphoserine phosphatase-1 (SHP-1) on epithelial barrier integrity. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Barrier function was detected by trans-epithelial electrical resistance (TEER) and FITC-dextran assay. The expression levels of SHP-1, phosphorylation signal transducer and activator of transcription 3 (p-STAT3), STAT3 and tight junction proteins were measured by qRT-PCR or western blot. In vivo model of ulcerative colitis was established to detect the function of Luteolin in ulcerative colitis. Results We clarified that Luteolin protected intestinal epithelial barrier function of Caco-2 monolayers by increasing the resistance values and tight junction (TJ) protein expression. The expression of OCLN, CLDN1, and ZO1 was increased by Luteolin, while the expression of CLDN2 was decreased. Furthermore, Luteolin significantly alleviated the symptom of ulcerative colitis in DSS-induced mice. The in vitro cell model proved that overexpression of SHP-1 promotes the epithelial barrier function and knockdown of SHP-1 or STAT3 activation destroyed the protective effects of Luteolin on the expression of TJ proteins. Conclusion We found that the treatment of Luteolin promoted epithelial barrier function and Luteolin might preserve intestinal epithelial barrier function through suppression of STAT3 signaling pathway by SHP-1.
ISSN:1023-3830
1420-908X
DOI:10.1007/s00011-021-01468-9