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Purpose: Inflammatory conditions like inflammatory bowel diseases (IBD) are characterized by increased immune cell infiltration. The chemokine ligand CXCL1 and its receptor CXCR1 have been shown to be involved in leukocyte adhesion, transendothelial recruitment, and chemotaxis. Therefore, the objective of this study was to describe CX3CL1-CX3CR1-mediated signaling in the induction of immune cell recruitment during experimental murine colitis. Methods: Acute colitis was induced by dextran sodium sulfate (DSS), and sepsis was induced by injection of lipopolysaccharide (LPS). Serum concentrations of CXCR1 and CXCL1 were measured by ELISA. Wild-type and CXCR1 mice were challenged with DSS, and on day 6, intravital microscopy was performed to monitor colonic leukocyte and platelet recruitment. Intestinal inflammation was assessed by disease activity, histopathology, and neutrophil infiltration. Results: CXCR1 was upregulated in DSS colitis and LPS-induced sepsis. CXCR1 mice were protected from disease severity and intestinal injury in DSS colitis, and CXCR1 deficiency resulted in reduced rolling of leukocytes and platelets. Conclusions: In the present study, we provide evidence for a crucial role of CXCL1-CXCR1 in experimental colitis, in particular for intestinal leukocyte recruitment during murine colitis. Our findings suggest that CXCR1 blockade represents a potential therapeutic strategy for treatment of IBD. [ABSTRACT FROM AUTHOR]

Purpose: An herbal preparation, STW 5, used clinically in functional dyspepsia and irritable bowel syndrome, has been shown to possess properties that may render it useful in inflammatory bowel disease (IBD). The present work was conducted to study its effectiveness in a rat model of IBD. Methods: An experimental model reflecting ulcerative colitis in man was adopted, whereby colitis was induced in Wistar rats by feeding them 5 % dextran sulfate sodium (DSS) in drinking water for one week. STW 5 and sulfasalazine (as a reference standard) were administered orally daily for 1 week before colitis induction and continued during DSS feeding. The animals were then sacrificed, and the severity of colitis was evaluated macroscopically and microscopically. Colon samples were homogenized for determination of reduced glutathione, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-3 as well as myeloperoxidase, glutathione peroxidase, and superoxide dismutase. In addition, colon segments were suspended in an organ bath to test their reactivity towards carbachol, KCl, and trypsin. Results: STW 5 and sulfasalazine were both effective in preventing the shortening of colon length and the increase in both colon mass index and total histology score as well as the changes in biochemical parameters measured except changes in dismutase activity. DSS-induced colitis led to marked depression in colonic responsiveness to the agents tested ex vivo, an effect which was normalized by both drugs. Conclusions: The findings point to a potential usefulness of STW 5 in the clinical setting of ulcerative colitis. [ABSTRACT FROM AUTHOR]