title: Muramyl dipeptide mediated activation of human bronchial epithelial cells interacting with basophils: a novel mechanism of airway inflammation.
abstract: Respiratory tract bacterial infection can amplify and sustain airway inflammation. Intracytosolic nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is one member of the nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) family, which senses the conserved structural peptidoglycan component muramyl dipeptide (MDP) in almost all bacteria. In the present study, activation of the NOD2 ligand MDP on primary human bronchial epithelial cells (HBE) co-cultured with human basophils was investigated. Cytokines, NOD2, adhesion molecules and intracellular signalling molecules were assayed by enzyme-linked immunosorbent assay or flow cytometry. The protein expression of NOD2 was confirmed in basophils/KU812 cells and HBE/human bronchial epithelial cell line (BEAS-2B) cells. MDP was found to up-regulate significantly the cell surface expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 on basophils and HBE in the co-culture system with or without basophil priming by interleukin (IL)-33 (all P < 0·05). MDP could further enhance the release of inflammatory cytokine IL-6 and chemokine CXCL8, and epithelium-derived anti-microbial peptide β-defensin 2 in the co-culture. HBE cells were the major source for the release of IL-6, CXCL8 and β-defensin2 upon stimulation by MDP in the co-culture system. The expression of ICAM-1 and VCAM-1 and release of IL-6 and CXCL8 were suppressed by various signalling molecule inhibitors, implying that the interaction between basophils and primary human bronchial epithelial cells could be regulated differentially by the mitogen-activated protein kinase pathways and nuclear transcription factors. The results therefore provide a new insight into the functional role of basophils in innate immunity, and the link between respiratory bacteria-mediated innate immunity and subsequent amplification of allergic inflammation in the airway.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: H N
authors.initials: HN
authors.lastname: Qiu
authors.forename: C K
authors.initials: CK
authors.lastname: Wong
authors.forename: I M T
authors.initials: IM
authors.lastname: Chu
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.forename: C W K
authors.initials: CW
authors.lastname: Lam
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology / Q000494:pharmacology*; D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects* / Q000276:immunology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000201:enzymology / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology; D012141:Respiratory Tract Infections / Q000201:enzymology / Q000276:immunology; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology
chemical_list: C508606:CXCL8 protein, human; C106641:DEFB4A protein, human; C506536:IL33 protein, human; C508600:IL6 protein, human; D000067596:Interleukin-33; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D019010:Vascular Cell Adhesion Molecule-1; D023083:beta-Defensins; D018799:Intercellular Adhesion Molecule-1; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D020928:Mitogen-Activated Protein Kinases