Innate immune receptors in human airway smooth muscle cells: activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 agonists

• Published in: PloS one 2013-07, Vol.8 (7), p.e68701
• Main Authors: Månsson Kvarnhammar, Anne, Tengroth, Lotta, Adner, Mikael, Cardell, Lars-Olaf
• Format: Article
• Language: English
• Subjects: Activation; Adrenergic receptors; Aminoquinolines - pharmacology; Analysis; Asthma; Bacteria; Biology; Biomarkers - metabolism; Cell culture; Cell Proliferation; Cell surface; Cytokines - biosynthesis; Cytokines - immunology; Cytometry; Deoxyribonucleic acid; Disease control; DNA; Eotaxin; Flow cytometry; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Gram-negative bacteria; Granulocyte-macrophage colony-stimulating factor; Growth factors; Histocompatibility antigen HLA; Humans; Immune system; Immunity, Innate; Immunocytochemistry; Immunologi inom det medicinska området; Immunomodulation; Infections; Inflammation; Intercellular adhesion molecule 1; Interleukin 6; Interleukin 8; Klinisk medicin; Ligands; Lipopeptides - pharmacology; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lungmedicin och allergi; Medicin och hälsovetenskap; Medicine; Medicinska och farmaceutiska grundvetenskaper; Microorganisms; mRNA; Muscle contraction; Muscles; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - immunology; Myosin; Myosin-light-chain kinase; Nod Signaling Adaptor Proteins - agonists; Nod Signaling Adaptor Proteins - genetics; Nod Signaling Adaptor Proteins - immunology; Nod1 protein; NOD2 protein; Pattern recognition; Pattern recognition receptors; Poly I-C - pharmacology; Polymerase chain reaction; Proteins; Receptors; Respiratory tract; Respiratory tract diseases; RNA, Messenger - genetics; RNA, Messenger - immunology; Rodents; Signal Transduction; Smooth muscle; Stimulation; Surface markers; Toll-Like Receptors - agonists; Toll-Like Receptors - genetics; Toll-Like Receptors - immunology; Trachea - cytology; Trachea - drug effects; Trachea - immunology; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068701

Pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs), recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs). Expression of TLR, NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow cytometry and immunocytochemistry. The functional responses to ligand stimulation were investigated in terms of cytokine and chemokine release, cell surface marker expression, proliferation and proteins regulating the contractile state. HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the corresponding agonists Pam3CSK4, poly(I:C), LPS, R-837 and iE-DAP, respectively, induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR, while poly(I:C) also affected the release of eotaxin and RANTES. The proliferative response was slightly increased by LPS. Stimulation, most prominently with poly(I:C), down-regulated myosin light chain kinase and cysteinyl leukotriene 1 receptor expression and up-regulated β2-adrenoceptor expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or RIG-I/MDA-5. Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a synthetic phenotype, characterized by an increased ability to release inflammatory mediators, acquire immunomodulatory properties by recruiting and interacting with other cells, and reduce the contractile state. The PRRs might therefore be of therapeutic use in the management of asthma and infection-induced disease exacerbations.