title: Innate immune receptors in human airway smooth muscle cells: activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 agonists.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Månsson Kvarnhammar
authors.forename: Lotta
authors.initials: L
authors.lastname: Tengroth
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
authors.forename: Lars-Olaf
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D000077271:Imiquimod; D007113:Immunity, Innate; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D053472:Nod Signaling Adaptor Proteins / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D000634:Aminoquinolines; D015415:Biomarkers; D016207:Cytokines; D055666:Lipopeptides; D008070:Lipopolysaccharides; D053472:Nod Signaling Adaptor Proteins; C508075:Pam(3)CSK(4) peptide; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D011070:Poly I-C; D000077271:Imiquimod