Bacteria- and host-derived mechanisms to control intestinal epithelial cell homeostasis: Implications for chronic inflammation

• Published in: Inflammatory bowel diseases Vol. 13; no. 9; pp. 1153 - 1164
• Main Authors: Clavel, Thomas, Haller, Dirk
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford University Press 01.09.2007; Wiley Subscription Services, Inc., A Wiley Company
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Bacteria; commensal bacteria; Crohn's disease; Data processing; Defense mechanisms; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; endoplasmic reticulum stress; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - metabolism; Feedback; Feedback, Physiological; Genetic Predisposition to Disease; glucose regulated protein (Grp)‐78; Heat-Shock Proteins - metabolism; Homeostasis; host‐derived anti‐inflammatory signals; Humans; Immune response; Inflammation - genetics; Inflammatory bowel diseases; Inflammatory Bowel Diseases - metabolism; Interleukin 10; Interleukin-10 - metabolism; intestinal epithelial cells; Intestine; Molecular Chaperones - metabolism; Mucosal immunity; NF- Kappa B protein; NF-kappa B - metabolism; nuclear transcription factor κB (NF‐κB); Oligomerization; Pattern recognition; Protein Structure, Tertiary; Reviews; Signal transduction; Stress; Toll-like receptors; Toll-Like Receptors - metabolism; Transcription factors; Transforming growth factor; Transforming Growth Factor beta - metabolism; Ulcerative colitis; nuclear transcription factor κB (NF-κB); intestinal epithelial cells; host-derived anti-inflammatory signals; inflammatory bowel diseases; glucose regulated protein (Grp)-78; commensal bacteria; endoplasmic reticulum stress; interleukin 10
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1002/ibd.20174

The genetic predisposition to deregulated mucosal immune responses and the concurrent prevalence of certain environmental triggers in developed countries are strong etiologic factors for the development of inflammatory bowel diseases in human subjects, including Crohn's disease and ulcerative colitis. Numerous clinical and experimental studies have shown that the intestinal microbes are critical for the initiation and progression of chronic intestinal inflammation. Activation of pattern recognition receptor signaling via members of the Toll-like receptor (TLR) and the nucleotide-binding oligomerization domain (NOD)-like families initiates inflammatory defense mechanisms that are required to alert and protect the host. Key inflammatory mechanisms such as nuclear transcription factor κB (NF-κB) activation and endoplasmic reticulum stress responses are controlled by a complex network of pathways that includes intrinsic feedback effectors and is targeted by immunosuppressive cytokines such as interleukin 10 (IL-10) and transforming growth factor (TGF)-β. In the absence or after functional loss of these antiinflammatory feedback signals, physiological defense mechanisms may turn into pathological responses. The data discussed in the present review suggest that disturbances in the homeostasis between bacteria- and host-derived signals at the epithelial cell level lead to a break in the intestinal barrier function and to the development of mucosal immune disorders in genetically susceptible hosts.