Related Experiment Video
Updated: Jul 3, 2026
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Muramyldipeptide modulates CXCL-8 release of BEAS-2B cells via NOD2
L Farkas1, B Stoelcker, N Jentsch
1Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany. laszlo.farkas@klinik.uni-regensburg.de
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 enhance CXCL-8 release from otherwise unstimulated BEAS-2B cells, a 12 h 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 SNP13 mutant decreased MDP-induced chemokine production in BEAS-2B 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-2B cells following LPS-challenge via synergistic interactions between MDP and LPS.
Insights
Nucleotide oligomerization domain 2 (NOD2) and muramyldipeptide (MDP) are crucial for CXCL-8 release in bronchial cells. Their interaction with lipopolysaccharide (LPS) influences immune responses in chronic obstructive pulmonary disease (COPD).
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Chronic obstructive pulmonary disease (COPD) involves chronic inflammation and impaired immune responses.
- Nucleotide oligomerization domain 2 (NOD2) is an innate immune receptor for muramyldipeptide (MDP), and its dysfunction is linked to inflammatory diseases.
- NOD2 gene mutations can lead to decreased MDP recognition, contributing to intestinal inflammation and pulmonary complications.
Purpose of the Study:
- To investigate the role of NOD2, toll-like receptor 4 (TLR4), and receptor-interacting protein 2 (RIP2) in bronchial epithelial cells.
- To elucidate the mechanisms by which tumor-necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) influence these immune receptors.
- To examine the synergistic effects of MDP and lipopolysaccharide (LPS) on CXCL-8 chemokine release.
Main Methods:
- Utilized the bronchial epithelial cell line BEAS-2B.
- Investigated the induction of NOD2, TLR4, and RIP2 by TNF-alpha and IFN-gamma.
- Assessed the impact of LPS on NOD2 transcription in cytokine-primed cells.
- Measured CXCL-8 release following stimulation with MDP and/or LPS.
- Compared chemokine production in cells overexpressing wild-type NOD2 versus an SNP13 mutant.
Main Results:
- TNF-alpha and IFN-gamma induce NOD2, TLR4, and RIP2 in BEAS-2B cells.
- LPS further increases NOD2 transcription in cytokine-activated cells.
- MDP alone does not enhance CXCL-8 release, but primes cells for increased secretion after TNF-alpha/IFN-gamma pre-stimulation via NOD2/RIP2.
- LPS significantly increases CXCL-8 production, with MDP co-administration further augmenting secretion.
- Overexpression of an SNP13 NOD2 mutant reduces MDP-induced chemokine production compared to wild-type NOD2.
Conclusions:
- MDP and NOD2 play a significant role in CXCL-8 release from bronchial epithelial cells upon LPS challenge.
- Synergistic interactions between MDP and LPS are critical for modulating immune responses in the airways.
- These findings highlight the complex interplay of innate immune receptors and bacterial components in COPD pathogenesis.
More Related Videos
10:12Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells
Published on: July 14, 2020
08:47Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016