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MIP-3α Expression in Macrophages Is NOD Dependent

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-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 (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-3α secretion in MONO-MAC-6 (MM6) cells. MIP-3α 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-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.

Authors: Hausmann M, Zeitler C, Weber A, Krebs M, Kellermeier S, Rosenstiel P, de Valliere C, Kosovac K, Fried M, Holler E, Rogler G.
Journal: Digestion. ;85(3):192-201
Year: 2012
PubMed: Find in PubMed