Rogler, Gerhard and Gelbmann, C. M. and Vogl, D. and Brunner, M. and Schoelmerich, Juergen and Falk, W. and Andus, T. and Brand, K. (2001) Differential activation of cytokine secretion in primary human colonic fibroblast/myofibroblast cultures. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 36 (4). pp. 389-398. ISSN 0036-5521
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Background: Fibroblasts and myofibroblasts are known to secrete a wide spectrum of cytokines, but the individual spectrum is tissue-specific. We investigated the effect of cell activation on cytokine secretion of isolated human colonic fibroblasts/myofibroblasts from control patients and patients with mucosal inflammation. Methods: Primary cultures of human colonic submucosal fibroblasts/myofibroblasts were incubated with IL-1 alpha (100 U/ml), IL-1 beta (10 ng/ml), IL-10 (10 ng/ml), TNF (10 ng/ml), PMA (10 ng/ml), LPS (50 ng/ml), IL-4 (10 ng/ml), or a combination of EL-I and TNF. Secreted cytokines were determined by ELISA. NF-kappaB activation was demonstrated by electrophoretic mobility-shift assays (EMSA). Results: Incubation of colonic fibroblasts/myofibroblasts with IL-1, LPS, TNF and PMA induced secretion of IL-6, IL-8, M-CSF and GM-CSF. IL-8 and IL-6 secretion could be stimulated by IL-1 alpha, IL-1 beta, TNF, PMA and LPS within 6 h of incubation. IL-6 secretion was stimulated from 0.5 +/- 0.01 pg/h x mug fibroblast protein to 18.5 +/- 2.6 pg/h x mug fibroblast protein with IL-1 beta (P < 0.01). IL-8 secretion was stimulated from 1.0 <plus/minus> 0.1 pg/h x mug fibroblast protein to 41.1 +/- 3.6 pg/h x pg (P < 0.005). IL-4 and IL-10 did not change cytokine secretion significantly. No significant differences between cultures from normal and inflamed mucosa were observed. TNF and IL-1 induced NF-<kappa>B activation. ALLN, a proteasome and NF-kappaB activation inhibitor, reduced TNF-mediated IL-8, GM-CSF and M-CSF induction significantly, whereas induction of IL-6 secretion remained unchanged. Conclusion: Human colonic myofibroblasts can secrete large amounts of IL-6, IL-8, M-CSF and GM-CSF upon stimulation. The induction of IL-8, M-CSF and GM-CSF, but not of IL-6 secretion, is mediated mainly by NF-kappaB activation. The cytokine profile and the total amounts of cytokines released suggest that colonic myofibroblasts can play a role in leukocyte recruitment and during mucosal inflammation. They therefore have to be regarded as an important part of the mucosal immune system.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY BOWEL-DISEASE; SMOOTH MUSCLE ACTIN; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; INTERLEUKIN-6 GENE; TNF-ALPHA; EXPRESSION; FIBROBLASTS; IBD; myofibroblasts; NF-kappa B; IL-8; IL-6 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Feb 2022 09:09 |
| Last Modified: | 08 Feb 2022 09:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/41626 |
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