TLR3 activation increases chemokine expression in human fetal airway smooth muscle cells

Arij Faksh, Rodney Jr. Britt, Elizabeth R. Vogel, Michael A. Thompson, Hitesh C. Pandya, Richard J. Martin, Christina M Pabelick, Y.s. Prakash

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Viral infections, such as respiratory syncytial virus and rhinovirus, adversely affect neonatal and pediatric populations, resulting in significant lung morbidity, including acute asthma exacerbation. Studies in adults have demonstrated that human airway smooth muscle (ASM) cells modulate inflammation through their ability to secrete inflammatory cytokines and chemokines. The role of ASM in the developing airway during infection remains undefined. In our study, we used human fetal ASM cells as an in vitro model to examine the effect of Toll-like receptor (TLR) agonists on chemokine secretion. We found that fetal ASM express multiple TLRs, including TLR3 and TLR4, which are implicated in the pathogenesis of respiratory syncytial virus and rhinovirus infection. Cells were treated with TLR agonists, polyinosinic-polycytidylic acid [poly(I:C)] (TLR3 agonist), lipopolysaccharide (TLR4 agonist), or R848 (TLR7/8 agonist), and IL-8 and chemokine (C-C motif) ligand 5 (CCL5) secretion were evaluated. Interestingly, poly(I:C), but neither lipopolysaccharide nor R848, increased IL-8 and chemokine (C-C motif) ligand 5 secretion. Examination of signaling pathways suggested that the poly(I:C) effects in fetal ASM involve TLR and ERK signaling, in addition to another major inflammatory pathway, NF-_B. Moreover, there are variations between fetal and adult ASM with respect to poly(I:C) effects on signaling pathways. Pharmacological inhibition suggested that ERK pathways mediate poly(I:C) effects. Overall, our data show that poly(I:C) initiates activation of proinflammatory pathways in developing ASM, which may contribute to immune responses to infection and exacerbation of asthma.

Original languageEnglish (US)
Pages (from-to)L202-L211
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number2
DOIs
StatePublished - 2016

Fingerprint

Poly C
Chemokines
Smooth Muscle Myocytes
Smooth Muscle
Toll-Like Receptors
resiquimod
Rhinovirus
CC Chemokines
Interleukin-8
Lipopolysaccharides
Asthma
Ligands
Poly I-C
Respiratory Syncytial Virus Infections
Respiratory Syncytial Viruses
MAP Kinase Signaling System
Virus Diseases
Infection
Pharmacology
Pediatrics

Keywords

  • Airway
  • Asthma
  • Chemokine
  • Development
  • Inflammation
  • Tolllike receptor
  • Virus

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

TLR3 activation increases chemokine expression in human fetal airway smooth muscle cells. / Faksh, Arij; Britt, Rodney Jr.; Vogel, Elizabeth R.; Thompson, Michael A.; Pandya, Hitesh C.; Martin, Richard J.; Pabelick, Christina M; Prakash, Y.s.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 310, No. 2, 2016, p. L202-L211.

Research output: Contribution to journalArticle

Faksh, Arij ; Britt, Rodney Jr. ; Vogel, Elizabeth R. ; Thompson, Michael A. ; Pandya, Hitesh C. ; Martin, Richard J. ; Pabelick, Christina M ; Prakash, Y.s. / TLR3 activation increases chemokine expression in human fetal airway smooth muscle cells. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2016 ; Vol. 310, No. 2. pp. L202-L211.
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AU - Britt, Rodney Jr.

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AU - Pandya, Hitesh C.

AU - Martin, Richard J.

AU - Pabelick, Christina M

AU - Prakash, Y.s.

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