Hausmann, M. and Zeitler, C. and Weber, A. and Krebs, M. and Kellermeier, S. and Rosenstiel, P. and de Valliere, C. and Kosovac, K. and Fried, M. and Holler, E. and Rogler, G. (2012) MIP-3 alpha Expression in Macrophages Is NOD Dependent. DIGESTION, 85 (3). pp. 192-201. ISSN 0012-2823,
Full text not available from this repository. (Request a copy)Abstract
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-kappa B (NF-kappa B). Upon NF-kappa B activation, intestinal macrophages (IMACs) induce expression of macrophage inflammatory protein (MIP)-3 alpha to attract memory T lymphocytes. We therefore investigated the influence of NOD2 ligation of IMAC differentiation and functional MIP-3 alpha induction. Methods: Human embryonal kidney HEK293 cells were transfected with NOD2 wildtype (NOD2(WT)) and the NOD2 SNP13 variant (NOD2(L1007fsinsC)) 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-3 alpha secretion in MONO-MAC-6 (MM6) cells. MIP-3 alpha mRNA was also significantly (* p < 0.05) induced in HEK293 transfected with NOD2(WT) 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-3 alpha secretion in the human myeloid cell line MM6 upon MDP. However, MIP-3 alpha-driven recruitment of Th17 cells or CD45R0(+) memory T lymphocytes is not affected in patients carrying heterozygous NOD2 variants. Copyright (C) 2012 S. Karger AG, Basel
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY PROTEIN 3-ALPHA; NF-KAPPA-B; TRANSPORTS MURAMYL DIPEPTIDE; INTESTINAL EPITHELIAL-CELLS; CC-CHEMOKINE RECEPTOR; NECROSIS-FACTOR-ALPHA; CROHNS-DISEASE; DENDRITIC CELLS; BOWEL-DISEASE; ACTIVATED RECEPTORS; Monocytes/macrophages; NOD2/CARD15; MIP-3 alpha expression; Inflammatory bowel disease |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 May 2020 06:40 |
| Last Modified: | 25 May 2020 06:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19489 |
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