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The Gut - Bad and Ugly Maria Lawrenz

The Gut - Bad and Ugly Maria Lawrenz. http://www.hillsboro.k12.mo.us/faculty/link_robin/intestines.html. The mucosal immune system. Protection from pathogenic infection Responsiveness. Coexistence with commensal flora Non-responsiveness . IBD. Ulcerative Colitis (UC) Restricted to colon

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The Gut - Bad and Ugly Maria Lawrenz

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  1. The Gut - Bad and UglyMaria Lawrenz http://www.hillsboro.k12.mo.us/faculty/link_robin/intestines.html

  2. The mucosal immune system Protection from pathogenic infection Responsiveness Coexistence with commensal flora Non-responsiveness IBD

  3. Ulcerative Colitis (UC) • Restricted to colon • Th2 response • (IL4, IL5, IL13) • Crohn Disease (CD) • terminal ileum, cecum, perianal area, colon • Th1 response • (IL12/IL23, TNFα, IFNγ/IL17) Inflammatory Bowel Disease (IBD) Chronic inflammation of the gut Unknown aetiology ( Genetic and environmental factors ) Symptoms: diarrhoea, abdominal pain, weight loss Treatment: Corticosteroids, Antibiotics, Infliximab (anti-TNFa antibody), Surgery (resection of affected part)

  4. Components of bacterial cell wall TPL-2 Role of TPL-2 in IBD Proinflammatory cytokines and chemokines TPL-2/ERK signalling pathway

  5. CD UC Tumor control TPL-2/ ERK activation in patients with Crohn‘s Disease

  6. ** TC UC CD TPL-2 P-ERK 1/2 GAPDH ERK 1/2 GAPDH TPL-2/ ERK in patients with IBD ** ** p<0,005

  7. DSS • Disruption of epithelial barrier • Activation of immune system 3% DSS TPL-2/ERK in experimental colitis (modified)

  8. 3% DSS TPL-2 deficient mice (TPL-2 KO)

  9. Cytokine production in colon culture d8 post DSS Less inflammation in TPL-2 KO  Histology ( Infiltration of immune cells)

  10. Open questions / future directions • Mechanisms of TPL-2 regulation of cytokines • DSS colitis + TPL-2 inhibitor treatment

  11. Many thanks for CNV support! Ulrich Steinhoff SHE Kaufmann

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