0000000000372875
AUTHOR
G. Schürmann
Cytokine Gene Transcription By NF-kappaB Family Members in Patients with Inflammatory Bowel Disease
We examined the expression of the transcription factor NF-kappa B, a nuclear trans-acting factor known to play a key role in cytokine gene regulation, in patients with inflammatory bowel disease (IBD). It was found that LP macrophages in Crohn's disease (CD) and ulcerative colitis (UC) display high levels of NF-kappa B DNA-binding activity accompanied by an increased production of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) alpha. Western blot studies showed an increased expression of the p50 and c-rel subunits of NF-kappa B; however, the most striking finding was an increased expression level of NF-kappa B p65 in patients with CD and UC. Selective downregulation of p65 in IBD…
Zur Immunpathogenese der chronisch entz�ndlichen Darmerkrankungen
Die chronisch entzundlichen Darmerkrankungen (CED: Morbus Crohn, Colitis ulcerosa) sind durch schubartig verlaufende destruierende Entzundungsreaktionen der Darmschleimhaut gekennzeichnet. In den letzten Jahren konnte gezeigt werden, das bei diesen Erkrankungen eine pathologische Aktivierung des intestinalen Immunsystems durch mucosale Antigene auftritt. In der chronischen Phase der Erkankungen sowie bei der Entwicklung postoperativer Rezidive sind Anderungen in der Zellmigration sowie der Cytokinproduktion intestinaler Zellen wahrscheinlich von entscheidender Bedeutung. Basierend auf diesen neuen pathogenetischen Erkenntnissen werden zur Zeit innovative klinische Behandlungsstrategien gete…
Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn disease and experimental colitis in vivo
The pro-inflammatory cytokine interleukin (IL)-6 (refs. 1-5) can bind to cells lacking the IL-6 receptor (IL-6R) when it forms a complex with the soluble IL-6R (sIL-6R) (trans signaling). Here, we have assessed the contribution of this system to the increased resistance of mucosal T cells against apoptosis in Crohn disease (CD), a chronic inflammatory disease of the gastrointestinal tract. A neutralizing antibody against IL-6R suppressed established experimental colitis in various animal models of CD mediated by type 1 T-helper cells, by inducing apoptosis of lamina propria T cells. Similarly, specific neutralization of sIL-6R in vivo by a newly designed gp130-Fc fusion protein caused suppr…