Muramyldipeptide modulates CXCL-8 release of BEAS-2B cells via NOD2

Farkas, L. and Stoelcker, B. and Jentsch, N. and Heitzer, S. and Pfeifer, M. and Schulz, C. (2008) Muramyldipeptide modulates CXCL-8 release of BEAS-2B cells via NOD2. SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 68 (3). pp. 315-322. ISSN 0300-9475,

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Abstract

Chronic inflammation and acute exacerbations are pathophysiological features of chronic obstructive pulmonary disease (COPD). An impaired immune response to bacterial pathogens can contribute to both of them. Nucleotide oligomerization domain 2 (NOD2) is an intracellular receptor of innate immunity for muramyldipeptide (MDP). Mutations of the NOD2 gene followed by decreased recognition of MDP are associated with chronic intestinal inflammation and pulmonary complications of patients with allogenic stem cell transplant and sepsis. Our study provides evidence that NOD2, toll-like receptor 4 (TLR4) and the adapter protein receptor-interacting protein 2 (RIP2) are induced by tumor-necrosis factor-alpha (TNF-alpha,) and interferon-gamma (IFN-gamma) in the bronchial epithelial cell line BEAS-2B. We also demonstrate that lipopolysaccharide (LPS) can further increase NOD2 transcription in a TNF-alpha and IFN-gamma-induced activation state. In addition, we show that, while MDP fails to I enhance CXCL-8 release from otherwise unstimulated BEAS-213 cells a 12 11, prestimulation period with TNF-alpha and IFN-gamma primes the cells for an additional increase of CXCL-8 secretion via induction of NOD2 and RIP2. LPS itself significantly augments CXCL-8 production and co-administration of MDP further increases cytokine secretion. Finally, overexpression of an SNP 13 mutant decreased MDP-induced chemokine production in BEAS-213 cells compared with NOD2 wild type overexpression. Taken together, our work indicates that MDP and NOD2 play an important role for CXCL-8 release of BEAS-213 cells following LPS-challenge via synergistic interactions between MDP and LPS.

Item Type: Article
Uncontrolled Keywords: OBSTRUCTIVE PULMONARY-DISEASE; INTESTINAL EPITHELIAL-CELLS; CROHNS-DISEASE; MURAMYL DIPEPTIDE; NOD2/CARD15 MUTATIONS; TNF-ALPHA; EXPRESSION; ACTIVATION; INNATE; RIP2;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Oct 2020 08:33
Last Modified: 26 Oct 2020 08:33
URI: https://pred.uni-regensburg.de/id/eprint/30445

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