ABSTRACT
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.
Subject(s)
Colitis, Ulcerative/drug therapy , Luteolin/therapeutic use , Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism , STAT3 Transcription Factor/metabolism , Animals , Caco-2 Cells , Cell Membrane Permeability/drug effects , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Colon/drug effects , Colon/metabolism , Colon/pathology , Dextran Sulfate , Humans , Luteolin/pharmacology , Male , Mice, Inbred C57BL , Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics , Signal Transduction/drug effects , Tight Junction Proteins/genetics , Tight Junction Proteins/metabolismABSTRACT
In this work, we establish a so-called "system-bath entanglement theorem," for arbitrary systems coupled with Gaussian environments. This theorem connects the entangled system-bath response functions in the total composite space to those of local systems, as long as the interacting bath spectral densities are given. We validate the theorem with direct evaluation via the exact dissipaton-equation-of-motion approach. Therefore, this work enables various quantum dissipation theories, which originally describe only the reduced system dynamics, for their evaluations on the system-bath entanglement properties. Numerical demonstrations are carried out on the Fano interference spectroscopies of spin-boson systems.
