Lotz Michael, König Till, Ménard Sandrine, Gütle Dominique, Bogdan Christian, Hornef Mathias W
Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Clinic of Freiburg, Freiburg, Germany.
Immunology. 2007 Nov;122(3):306-15. doi: 10.1111/j.1365-2567.2007.02639.x. Epub 2007 May 18.
Cytokines with anti-inflammatory properties have been implicated in the prevention of inappropriate immune activation by commensal bacteria in the intestinal tract. Here, we analysed receptor expression, cellular signalling, and the inhibitory activity of interleukin (IL)-4, -10, -11, and -13 as well as of transforming growth factor-beta on lipopolysaccharide-mediated small intestinal epithelial cell activation. Only IL-4 and IL-13 had a significant inhibitory effect on chemokine secretion and nitric oxide (NO) production in differentiated and polarized cells. Reverse transcription-polymerase chain reaction of primary intestinal epithelial cells obtained by laser-microdissection confirmed expression of the type II IL-4 receptor consisting of the IL-4 receptor alpha and the IL-13 receptor alpha1. Also, IL-4 or IL-13 led to rapid signal transducer and activator of transcription 6 phosphorylation, diminished inducible NO synthase expression, and enhanced the antagonistic arginase 1 activity. In conclusion, cytokines such as IL-4 and IL-13 affect intestinal epithelial cells and exhibit a modulating activity on Toll-like receptor-4-mediated epithelial cell activation.
具有抗炎特性的细胞因子与预防肠道共生菌引起的不适当免疫激活有关。在此,我们分析了白细胞介素(IL)-4、-10、-11和-13以及转化生长因子-β对脂多糖介导的小肠上皮细胞激活的受体表达、细胞信号传导和抑制活性。只有IL-4和IL-13对分化和极化细胞中的趋化因子分泌和一氧化氮(NO)产生具有显著抑制作用。通过激光显微切割获得的原代肠上皮细胞的逆转录-聚合酶链反应证实了由IL-4受体α和IL-13受体α1组成的II型IL-4受体的表达。此外,IL-4或IL-13导致信号转导子和转录激活子6快速磷酸化,减少诱导型NO合酶表达,并增强拮抗性精氨酸酶1活性。总之,IL-4和IL-13等细胞因子影响肠上皮细胞,并对Toll样受体-4介导的上皮细胞激活表现出调节活性。