Measurement of the innate immune response in the airway

Allan R. Brasier, Yingxin Zhao

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
Pages233-254
Number of pages22
Volume795
DOIs
StatePublished - 2014

Publication series

NameAdvances in Experimental Medicine and Biology
Volume795
ISSN (Print)00652598

Keywords

  • Cytokine
  • Inflammation
  • Innate immunity
  • Interferon
  • Interferon response factor (IRF)
  • Nuclear factor- κB (NF-κB)
  • Pattern recognition receptor
  • Quantitative real-time PCR (Q-RT-PCR)
  • Selected reaction monitoring (SRM)

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine

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