title: Reduced toll-like receptor 4 and substance P gene expression is associated with airway bacterial colonization in children.
abstract: Neuro-immune interactions are increasingly relevant to human health and disease. The neuropeptide Substance P also has antibacterial activity and bears similarities to the innate immune antibacterial defensins. This suggests possible co-regulation of neuropeptide and innate immune mediators. In this study, non-bronchoscopic bronchoalveolar lavage (BAL) was performed on 69 children. BAL was examined for cellular profile, microbiology (bacteria, virus) and gene expression for TLRs 2, 3, 4; chemokine receptors (CCR3, CCR5, CXCR1); neurotrophins and neurokinin genes (TAC1, TAC3, CGRP, NGF). In children with bacterial colonization (n=10) there was an airway inflammatory response with increased BAL neutrophils, IL-8 protein, and CXCR1 expression. Substance P (TAC1) and TLR4 RNA expression were reduced in children with bacterial colonization. TLR3 mRNA was increased in 7.2% (n=5) children with rhinovirus, and there was a non-significant trend to increased TLR2. There is evidence for co-regulation of neurokinin (TAC1) and TLR4 gene expression in airway cells from children with airway bacterial colonization and their reduced expression may be associated with an impaired bacterial clearance.
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, John Hunter Hospital, New Lambton, Australia.
authors.forename: Terry V
authors.initials: TV
authors.lastname: Grissell
authors.forename: Anne B
authors.initials: AB
authors.lastname: Chang
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D000293:Adolescent; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D013373:Substance P / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D011498:Protein Precursors; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D015320:Tachykinins; D051193:Toll-Like Receptors; C044206:preprotachykinin; D013373:Substance P; D020780:Matrix Metalloproteinase 9