title: Qing Hua Chang Yin inhibits the LPS-induced activation of the IL-6/STAT3 signaling pathway in human intestinal Caco-2 cells.
abstract: Increasing evidence indicates that the pathogenesis of ulcerative colitis (UC) is highly regulated by the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway and its negative feedback regulator, suppressor of cytokine signaling 3 (SOCS3). Therefore, modulating the signaling feedback loop of IL-6/STAT3/SOCS3 may prove to be a novel therapeutic approach for the treatment of UC. Qing Hua Chang Yin (QHCY) is a traditional Chinese formulation that has long been used in clinic for the treatment of UC. We have previously reported that QHCY ameliorates acute intestinal inflammation in vivo and in vitro through the suppression of the nuclear factor-κB (NF-κB) pathway. In the present study, in order to further elucidate the mechanisms responsible for the anti-inflammatory activities of QHCY, we stimulated human intestinal Caco-2 cells with lipopolysaccharide (LPS) to create an in vitro model of an inflamed human intestinal epithelium, and evaluated the effects of QHCY on the IL-6/STAT3/SOCS3 signaling network in inflamed Caco-2 cells. The levels of IL-6 were measured by ELISA and the levels of STAT3 and SOCS3 were measured by western blot analysis. We found that QHCY significantly inhibited the LPS-induced secretion of pro-inflammatory IL-6 in the Caco-2 cells in a dose-dependent manner. Moreover, QHCY profoundly suppressed the LPS-induced phosphorylation of Janus-activated kinase 1 (JAK1), JAK2 and STAT3. Furthermore, treatment with QHCY markedly augmented the expression of SOCS3. Taken together, the findings of the present study suggest that the modulation of the IL-6/STAT3/SOCS3 signaling network may be one of the mechanisms through which QHCY exerts its anti-inflammatory effects.
authors: Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors: Xiao
authors: X
authors: Ke
authors: Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors: Guanghong
authors: G
authors: Hu
authors: Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors: Wenyi
authors: W
authors: Fang
authors: Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors: Jintuan
authors: J
authors: Chen
authors: Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors: Xin
authors: X
authors: Zhang
authors: Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors: Chunbo
authors: C
authors: Yang
authors: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Minhou Shangjie, Fuzhou, Fujian 350122, P.R. China.
authors: Jun
authors: J
authors: Peng
authors: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors: Youqin
authors: Y
authors: Chen
authors: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors: Thomas J
authors: TJ
authors: Sferra
mesh_terms: D018938:Caco-2 Cells; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D008070:Lipopolysaccharides; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases