Bo-Lin Li1, Dan-Yang Zhao1, Peng-Li Du1, Xiao-Tian Wang1, Qian Yang2, Yan-Ru Cai3. 1. Department of Gastroenterology, Hebei Provincial Hospital of Chinese Medicine, No. 389, Zhongshan East Road, Chang an District, Shijiazhuang, 050011, Hebei, People's Republic of China. 2. Department of Gastroenterology, Hebei Provincial Hospital of Chinese Medicine, No. 389, Zhongshan East Road, Chang an District, Shijiazhuang, 050011, Hebei, People's Republic of China. yangmenhaha@163.com. 3. Department of Gastroenterology, Hebei Provincial Hospital of Chinese Medicine, No. 389, Zhongshan East Road, Chang an District, Shijiazhuang, 050011, Hebei, People's Republic of China. 137544977@qq.com.
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.
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.
Authors: Siew C Ng; Whitney Tang; Jessica Y Ching; May Wong; Chung Mo Chow; A J Hui; T C Wong; Vincent K Leung; Steve W Tsang; Hon Ho Yu; Mo Fong Li; Ka Kei Ng; Michael A Kamm; Corrie Studd; Sally Bell; Rupert Leong; H Janaka de Silva; Anuradhani Kasturiratne; M N F Mufeena; Khoon Lin Ling; Choon Jin Ooi; Poh Seng Tan; David Ong; Khean L Goh; Ida Hilmi; Pises Pisespongsa; Sathaporn Manatsathit; Rungsun Rerknimitr; Satimai Aniwan; Yu Fang Wang; Qin Ouyang; Zhirong Zeng; Zhenhua Zhu; Min Hu Chen; Pin Jin Hu; Kaichun Wu; Xin Wang; Marcellus Simadibrata; Murdani Abdullah; Justin Cy Wu; Joseph J Y Sung; Francis K L Chan Journal: Gastroenterology Date: 2013-04-09 Impact factor: 22.682
Authors: Antonio Speciale; Claudia Muscarà; Maria Sofia Molonia; Giovanni Toscano; Francesco Cimino; Antonella Saija Journal: Front Pharmacol Date: 2022-02-11 Impact factor: 5.810