| Autor: |
Hausmann, M., Zeitler, C., Weber, A., Krebs, M., Kellermeier, S., Rosenstiel, P., de Vallière, C., Kosovac, K., Fried, M., Holler, E., Rogler, G. |
| Předmět: |
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| Zdroj: |
Digestion; 2012, Vol. 85 Issue 3, p192-201, 10p, 2 Color Photographs, 1 Chart, 3 Graphs |
| Abstrakt: |
Background: The first identified susceptibility gene for Crohn's disease, NOD2, acts as a sensor for the bacterial-wall peptidoglycan fragment muramyl dipeptide (MDP) and activates the transcription factor nuclear factor-κB (NF-κB). Upon NF-κB activation, intestinal macrophages (IMACs) induce expression of macrophage inflammatory protein (MIP)-3α to attract memory T lymphocytes. We therefore investigated the influence of NOD2 ligation of IMAC differentiation and functional MIP-3α induction. Methods: Human embryonal kidney HEK293 cells were transfected with NOD2 wild-type (NOD2WT) and the NOD2 SNP13 variant (NOD2L1007fsinsC) and stimulated with MDP. Recruitment of CD45R0+ and Th17 cells was determined by immunohistochemistry. Results: Endogenous NOD2 stimulation was followed by a dose-dependent increase in MIP-3α secretion in MONO-MAC-6 (MM6) cells. MIP-3α mRNA was also significantly (* p < 0.05) induced in HEK293 transfected with NOD2WT via MDP ligation. In vivo cell-cell contacts between IMACs and CD45R0+ memory T cells as well as recruitment of Th17 cells in patients of NOD2 variants were unchanged as compared to wild-type patients. Conclusion: Our data demonstrate a dose-dependent increase in MIP-3α secretion in the human myeloid cell line MM6 upon MDP. However, MIP-3α-driven recruitment of Th17 cells or CD45R0+ memory T lymphocytes is not affected in patients carrying heterozygous NOD2 variants. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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