Differential Activation of Cytokine Secretion in Primary Human Colonic Fibroblast/Myofibroblast Cultures
| Autor: | J. Schölmerich, Gerhard Rogler, K Brand, Cornelia M. Gelbmann, M Brunner, Tilo Andus, Daniela Vogl, Werner Falk |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Electrophoresis Lipopolysaccharides Male Colon medicine.medical_treatment Enzyme-Linked Immunosorbent Assay Biology Sensitivity and Specificity Crohn Disease Reference Values medicine Humans Secretion Intestinal Mucosa Fibroblast Cells Cultured Probability Analysis of Variance Tumor Necrosis Factor-alpha Biopsy Needle NF-kappa B Gastroenterology Fibroblasts Middle Aged Immunohistochemistry Interleukin-10 Interleukin 10 Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Cytokine Immunology Cancer research Cytokines Colitis Ulcerative Female Cytokine secretion Cell activation Myofibroblast Interleukin-1 medicine.drug |
| Zdroj: | Scandinavian Journal of Gastroenterology. 36:389-398 |
| ISSN: | 0036-5521 |
| DOI: | 10.1080/003655201300051216 |
| Popis: | 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.Primary cultures of human colonic submucosal fibroblasts/myofibroblasts were incubated with IL-1alpha (100 U/ml), IL-Ibeta (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 IL-1 and TNF. Secreted cytokines were determined by ELISA. NF-kappaB activation was demonstrated by electrophoretic mobility-shift assays (EMSA).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-1alpha, IL-1beta, TNF, PMA and LPS within 6 h of incubation. IL-6 secretion was stimulated from 0.5 +/- 0.01 pg/h x microg fibroblast protein to 18.5 +/- 2.6 pg/h x microg fibroblast protein with IL-1beta (P0.01). IL-8 secretion was stimulated from 1.0 +/- 0.1 pg/h x microg fibroblast protein to 41.1 +/- 3.6 pg/h x microg (P0.005). 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-kappaB 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.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. |
| Databáze: | OpenAIRE |
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