Muramyl dipeptide mediated activation of human bronchial epithelial cells interacting with basophils: A novel mechanism of airway inflammation

H. N. Qiu, C. K. Wong, I. M.T. Chu, S. Hu, C. W.K. Lam

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Summary: 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.

Original languageEnglish (US)
Pages (from-to)81-94
Number of pages14
JournalClinical and Experimental Immunology
Volume172
Issue number1
DOIs
StatePublished - Apr 1 2013

Fingerprint

Acetylmuramyl-Alanyl-Isoglutamine
Basophils
Epithelial Cells
Inflammation
Nucleotides
Coculture Techniques
Interleukin-6
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Innate Immunity
Cytokines
Bacteria
Defensins
Peptidoglycan
Mitogen-Activated Protein Kinases
Interleukin-8
Bacterial Infections
Respiratory Tract Infections
Flow Cytometry
Transcription Factors

Keywords

  • Basophils
  • Epithelial cells
  • Infections
  • Pattern recognition receptors
  • Signalling/signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Muramyl dipeptide mediated activation of human bronchial epithelial cells interacting with basophils : A novel mechanism of airway inflammation. / Qiu, H. N.; Wong, C. K.; Chu, I. M.T.; Hu, S.; Lam, C. W.K.

In: Clinical and Experimental Immunology, Vol. 172, No. 1, 01.04.2013, p. 81-94.

Research output: Contribution to journalArticle

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