S C Bischoff1, G Sellge, M P Manns, A Lorentz. 1. Department of Gastroenterology and Hepatology, Medical School of Hannover, Germany. bischoff.stephan@mh-hannover.de
Abstract
BACKGROUND: During the last years, mast cells have been recognized as a potent cellular source of multiple cytokines. However, little is known about the regulation of cytokine production by mature human mast cells derived from mucosal sites. METHODS: Human mast cells were isolated from intestinal mucosa and cultured for 14 days in the presence of stem cell factor (SCF) alone or in combination with IL-4. Mast cells were then stimulated by IgE receptor cross-linking or bacterial infection and cytokine production was examined by RT-PCR and ELISA. RESULTS: We found that human intestinal mast cells produce proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6 without further stimulation. Stimulation of the cells with gram-negative bacteria (Escherichia coli and others) caused an upregulation of TNF-alpha expression. Following IgE receptor cross-linking, we found additional expression of the Th2 cytokines IL-3, IL-5 and IL-13. Interestingly, mRNA for IL-3, IL-5 and IL-13 was also expressed in unstimulated mast cells provided they were cultured in the presence of SCF and IL-4. Moreover, IL-4 rendered mast cells capable of releasing IL-5 in response to bacterial challenge. CONCLUSION: In the presence of the mast cell survival factor SCF, mature human mast cells produce predominantly proinflammatory cytokines, whereas in the presence of SCF and IL-4, mast cells produce not only proinflammatory but also Th2 cytokines. Copyright 2001 S. Karger AG, Basel
BACKGROUND: During the last years, mast cells have been recognized as a potent cellular source of multiple cytokines. However, little is known about the regulation of cytokine production by mature human mast cells derived from mucosal sites. METHODS:Human mast cells were isolated from intestinal mucosa and cultured for 14 days in the presence of stem cell factor (SCF) alone or in combination with IL-4. Mast cells were then stimulated by IgE receptor cross-linking or bacterial infection and cytokine production was examined by RT-PCR and ELISA. RESULTS: We found that human intestinal mast cells produce proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6 without further stimulation. Stimulation of the cells with gram-negative bacteria (Escherichia coli and others) caused an upregulation of TNF-alpha expression. Following IgE receptor cross-linking, we found additional expression of the Th2 cytokines IL-3, IL-5 and IL-13. Interestingly, mRNA for IL-3, IL-5 and IL-13 was also expressed in unstimulated mast cells provided they were cultured in the presence of SCF and IL-4. Moreover, IL-4 rendered mast cells capable of releasing IL-5 in response to bacterial challenge. CONCLUSION: In the presence of the mast cell survival factor SCF, mature human mast cells produce predominantly proinflammatory cytokines, whereas in the presence of SCF and IL-4, mast cells produce not only proinflammatory but also Th2 cytokines. Copyright 2001 S. Karger AG, Basel