Inflammatory bowel disease (1)

Human intestinal permeability.

The molecular cloning of the C5a receptor places this molecule in the superfamily of G-protein coupled receptors. This superfamily is characterized by the presence of signature motifs including seven hydrophobic domains which span the cell membrane and impart a predicted serpentine topology to the receptor proteins. The identification of other members of this family, including receptors for the chemokines IL-8 and Mip-1/Rantes, thrombin, formyl peptide, and platelet activating factor, provide new tools for understanding structure-function relationships relevant to the inflammatory process. This review focuses on the recent biological studies concerning the ligand C5a and its cellular receptor, the structure/activity relationships so far discerned, signal transduction mechanisms, progress toward identification of receptor antagonists, and some likely directions for future studies. Where appropriate, relevant work on related seven transmembrane segment receptors is discussed.

C5A Anaphylatoxin and Its Seven Transmembrane-Segment Receptor

https://www.gastrojournal.org/article/0016-5085(92)91182-4/pdf

Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification.

BACKGROUND: Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn's disease. AIM: To compare the secretion rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa from patients with Crohn's disease. RESULTS: Organ cultures of intestinal biopsy specimens taken from areas of affected mucosa from patients with Crohn's disease spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared with controls but also biopsy specimens taken in macroscopically and microscopically unaffected areas in the same patients. Concentrations of IL-1 beta and IL-6 measured in the supernatant fluid of biopsy cultures were positively correlated with the degree of tissue involvement measured by both endoscopic and histological grading. By contrast, TNF-alpha concentrations were not correlated to endoscopic and histological grading. CONCLUSIONS: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn's disease provide evidence for a sustained immune stimulation in Crohn's disease even in the absence of patent inflammation. The results shed a new light on the role of inflammatory cytokines in the onset of intestinal tissue damage in Crohn's disease and suggest that the range of intestinal lesions in Crohn's disease may be wider than suspected on the basis of regular endoscopic and histological examinations.

https://gut.bmj.com/content/gutjnl/39/5/684.full.pdf

Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease.

There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199005103221903

Roger Hällgren

Papers

Enhanced Local Production of Complement Components in the Small Intestines of Patients with Crohn's Disease