BACKGROUND & AIMS: In this study, we determined the signal transduction and functional consequences after ligand-specific activation of the fractalkine receptor CX3CR1 in human intestinal epithelial cells. METHODS: CX3CR1 expression in human colonic tissues and intestinal epithelial cell lines was determined by immunohistochemistry, immunoblotting, and reverse-transcription polymerase chain reaction. The regulation of mitogen-activated protein kinase (MAPK) activation was assessed by immunoblotting. Regulation of chemokine messenger RNA (mRNA) expression was determined by Northern blotting. NF-kappa B and p53 activation was assessed by electromobility shift assays. RESULTS: Fractalkine mediated the MEK-1 and G alpha i-dependent but phosphatidylinositol-3-kinase-independent activation of extracellular signal-regulated kinase-MAPK. Fractalkine activated NF-kappa B and p53 resulting in interleukin 8 and fractalkine mRNA expression. CX3CR1-mediated activation of intestinal epithelial cells was able to induce migration of human neutrophils into but not through the intestinal epithelial cell monolayer. CONCLUSIONS: CX3CR1 mediates distinct functional responses in intestinal epithelial cells, which include the autocrine regulation of cell-survival signals and activation of immune modulators, indicating a role of CX3CR1 in host defense mechanisms originating from the intestinal epithelium.
BACKGROUND & AIMS: In this study, we determined the signal transduction and functional consequences after ligand-specific activation of the fractalkine receptor CX3CR1 in human intestinal epithelial cells. METHODS:CX3CR1 expression in human colonic tissues and intestinal epithelial cell lines was determined by immunohistochemistry, immunoblotting, and reverse-transcription polymerase chain reaction. The regulation of mitogen-activated protein kinase (MAPK) activation was assessed by immunoblotting. Regulation of chemokine messenger RNA (mRNA) expression was determined by Northern blotting. NF-kappa B and p53 activation was assessed by electromobility shift assays. RESULTS:Fractalkine mediated the MEK-1 and G alpha i-dependent but phosphatidylinositol-3-kinase-independent activation of extracellular signal-regulated kinase-MAPK. Fractalkine activated NF-kappa B and p53 resulting in interleukin 8 and fractalkine mRNA expression. CX3CR1-mediated activation of intestinal epithelial cells was able to induce migration of human neutrophils into but not through the intestinal epithelial cell monolayer. CONCLUSIONS:CX3CR1 mediates distinct functional responses in intestinal epithelial cells, which include the autocrine regulation of cell-survival signals and activation of immune modulators, indicating a role of CX3CR1 in host defense mechanisms originating from the intestinal epithelium.
Authors: Teresa K Tarrant; Peng Liu; Rishi R Rampersad; Denise Esserman; Lisa R Rothlein; Roman G Timoshchenko; Marcus W McGinnis; David J Fitzhugh; Dhavalkumar D Patel; Alan M Fong Journal: Arthritis Rheum Date: 2012-05
Authors: Rebecca A Moyer; Michael K Wendt; Priscilla A Johanesen; Jerrold R Turner; Michael B Dwinell Journal: Lab Invest Date: 2007-06-18 Impact factor: 5.662
Authors: Miquel Sans; Silvio Danese; Carol de la Motte; Heitor S P de Souza; Brenda M Rivera-Reyes; Gail A West; Manijeh Phillips; Jeffry A Katz; Claudio Fiocchi Journal: Gastroenterology Date: 2006-10-12 Impact factor: 22.682
Authors: Christopher S Anderson; Tatiana Chirkova; Christopher G Slaunwhite; Xing Qiu; Edward E Walsh; Larry J Anderson; Thomas J Mariani Journal: J Virol Date: 2021-03-17 Impact factor: 5.103
Authors: Julia Diegelmann; Florian Beigel; Kathrin Zitzmann; Artur Kaul; Burkhard Göke; Christoph J Auernhammer; Ralf Bartenschlager; Helmut M Diepolder; Stephan Brand Journal: PLoS One Date: 2010-12-08 Impact factor: 3.240