title: Measurement of the innate immune response in the airway.
abstract: Asthma is an idiopathic disease associated with episodic inflammation and reversible airway obstruction that is triggered by environmental agents. Allergic and infectious agents trigger asthmatic exacerbations through the innate immune response (IIR). The IIR is activated by sentinel cells in the airways to elaborate inflammatory cytokines and protective mucosal interferons whose actions are designed to limit the spread of the organism, as well as to activate the adaptive immune response. We address the structure of the IIR pathway in sentinel cells of the airway and describe observations on its dysregulation. The IIR is triggered in a cell-type specific manner by germline-encoded pathogen recognition receptors (PPRs) including plasma membrane Toll-like receptors (TLRs) and the cytoplasmic Retinoic Acid-inducible Gene (RIG)-I-like RNA helicases, and protein kinase R (PKR). Although their mechanisms of intracellular signaling differ, both pathways converge on a small group of transcriptional effectors, nuclear factor-κB (NF-κB), IFN regulatory factor (IRF), and signal transducer and activator of transcription (STAT). We describe several distinct techniques to quantitate the IIR including assays based on quantitative real-time PCR (Q-RT-PCR) of NF-κB and IRF3-regulated genes, multiplex bead-based analysis of secreted proteins/cytokines and more recent developments in targeted, quantitative selected reaction monitoring (SRM)-mass spectrometry (MS). Application of these methods for quantitation of the IIR will further our understanding of the role of the IIR in asthma and its contribution to disease heterogeneity.
authors.affiliation: University of Texas Medical Branch, 8.128 Medical Research Building, 301 University Blvd, Galveston, TX, USA, arbrasie@utmb.edu.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Brasier
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D056704:Adaptive Immunity; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D012720:Severity of Illness Index; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D019892:eIF-2 Kinase / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D019892:eIF-2 Kinase; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases