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Comment
. 2005 Feb;54(2):314-5; author reply 316-6.

Differential modulation of p38 mitogen activated protein kinase and STAT3 signalling pathways by infliximab and etanercept in intestinal T cells from patients with Crohn's disease

Comment

Differential modulation of p38 mitogen activated protein kinase and STAT3 signalling pathways by infliximab and etanercept in intestinal T cells from patients with Crohn's disease

P Rosenstiel et al. Gut. 2005 Feb.
No abstract available

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Figures

Figure 1
Figure 1
Intestinal CD4+ T cells were obtained from colonic biopsies from five patients with Crohn’s disease (median age 34 years (range 18–49)) with an established diagnosis of Crohn’s disease based on histopathological and endoscopic criteria. All patients had active disease at inclusion and were treated with 5-ASA (2–4 g/day, five patients), prednisone (20 mg/day, one patient), and azathioprine (150–200 mg/day, four patients). None of the patients had received anti-TNF-α treatment. Neither antigen nor feeder cells were added to the intestinal T cells cultures, which consisted of more than 97% CD3+/CD4+ T cells. (A) Infliximab, but not etanercept, activated p38α and induced apoptosis in intestinal T lymphocytes from Crohn’s disease patients. Levels of (phosphorylated) p38 mitogen activated protein kinase (MAPK) and PARP in in situ activated intestinal T lymphocytes were investigated by western blot 24 hours after stimulation with the respective TNF-α binding agent, as described previously. Data are representative of experiments performed in all patients, n = 5. (B) Signal transducer and activator of transcription 3 (STAT3) was activated in CD4+ cells in the intestinal mucosa in Crohn’s disease patients in vivo and downregulated by both infliximab and etanercept in intestinal T cells from Crohn’s disease patients in vitro. Western blot and immunofluorescence staining were performed as described previously. Filled arrowheads, cells positive for phospho-Y-STAT3 (anti-phospho-Y-STAT3, 1/100; Cell Signaling Technology) and CD4 (anti-CD4, 1/500; BD PharMingen, San Diego, California, USA); open arrowhead, CD4 immunoreactivity only (n = 5 for immunofluorescence and western blot; representative result for all experiments).

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