Rhinovirus elicits proasthmatic changes in airway responsiveness independently of viral infection

Grunstein, Michael; Hákonarson, Hákon; Whelan, Russell S.; Yu, Zheya Jenny; Grunstein, Judith S.; Chuang, Sing

doi:10.1067/mai.2001.120276

Cited by 41 publications

(28 citation statements)

References 28 publications

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“…Discrepancies have been noted between the magnitude of in vivo and in vitro responses to RV infection [Jarjour et al, 2000;Subauste and Proud, 2001], RV induces pro-inflammatory mediators from monocytes and smooth muscle cells [Gern et al, 1996;Grunstein et al, 2001] and non-ciliated cells derived from nasopharyngeal tissue could be infected with RV [Arruda et al, 1995]. We have also detected the presence of RV in sub-epithelial cells by in situ hybridization [Bardin et al, 1994].…”

Section: Introductionmentioning

confidence: 69%

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Ghildyal

Dagher

Donninger

et al. 2005

Journal of Medical Virology

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The events linking rhinovirus (RV) infection to airway symptoms are poorly understood. The virus initially infects airway epithelium followed by a vigorous inflammatory response that may entail spread of RV from epithelium to other cells in the airway wall. However, RV has fastidious growth characteristics and to date reproductive infection of primary cells other than human airway epithelium has not been confirmed. Airway fibroblasts are adjacent to and in contact with epithelial cells, play a key role in innate immune responses, and may participate in the evolution of inflammation. To investigate fibroblast actions, we first determined whether RV could infect and replicate in primary culture human lung fibroblasts. RV serotype 16 (RV16) was used to infect fibroblasts grown from lung tissue, and virus infection with replication was demonstrated by a combination of techniques. RT-PCR was used to show an increase in RV transcription; confocal microscopy demonstrated colocalization of the replicative form of RV genome (double-stranded RNA) and RV16 proteins; infectious virus was also recovered from the culture supernatant of infected fibroblasts. Functional consequences of RV infection were next examined. RV infection of fibroblasts was followed by an increase in epithelial neutrophil-activating peptide-78 (ENA-78) mRNA and protein. The permeability factor vascular endothelial growth factor (VEGF) was also induced over a similar time course. These data suggest that interactions between RV and human fibroblasts are feasible, may coordinate neutrophil chemoattraction with enhanced vascular permeability and that fibroblasts may contribute to inflammatory responses following RV infections.

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Section: Introductionmentioning

confidence: 69%

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Ghildyal

Dagher

Donninger

et al. 2005

Journal of Medical Virology

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“…More importantly, in studies with HRV16, a physiologically relevant ligand for airway epithelial ICAM-1, we identified Syk to be important for p38 activation. Previous studies in different cell populations that include airway epithelial cells (9), airway smooth muscle cells (42), alveolar macrophages, and human monocytes (6) have shown that HRV-induced p38 activation is dependent on HRV-ICAM-1 binding and that p38 activation is required for induction of inflammatory cytokine expression. Our observations confirm and enhance these studies, identifying a role for Syk in mediating ICAM-1 activation of p38 and IL-8 gene expression, and thus strongly suggest a role for the kinase in modulating the airway epithelial inflammatory response following HRV infection.…”

Section: Discussionmentioning

confidence: 99%

Syk Is Downstream of Intercellular Adhesion Molecule-1 and Mediates Human Rhinovirus Activation of p38 MAPK in Airway Epithelial Cells

Wang¹,

Lau²,

Wiehler

et al. 2006

The Journal of Immunology

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The airway epithelium is the primary target of inhaled pathogens such as human rhinovirus (HRV). Airway epithelial cells express ICAM-1, the major receptor for HRV. HRV binding to ICAM-1 mediates not only viral entry and replication but also a signaling cascade that leads to enhanced inflammatory mediator production. The specific signaling molecules and pathways activated by HRV-ICAM-1 interactions are not well characterized, although studies in human airway epithelia implicate a role for the p38 MAPK in HRV-induced cytokine production. In the current study, we report that Syk, an important immunoregulatory protein tyrosine kinase, is highly expressed by primary and cultured human airway epithelial cells and is activated in response to infection with HRV16. Biochemical studies revealed that ICAM-1 engagement by HRV and cross-linking Abs enhanced the coassociation of Syk with ICAM-1 and ezrin, a cytoskeletal linker protein. In polarized airway epithelial cells, Syk is diffusely distributed in the cytosol under basal conditions but, following engagement of ICAM-1 by cross-linking Abs, is recruited to the plasma membrane. The enhanced Syk-ICAM-1 association following HRV exposure is accompanied by Syk phosphorylation. ICAM-1 engagement by HRV and cross-linking Abs also induced phosphorylation of p38 in a Syk-dependent manner, and conversely, knockdown of Syk by short interfering (si)RNA substantially diminished p38 activation and IL-8 gene expression. Taken together, these observations identify Syk as an important mediator of the airway epithelial cell inflammatory response by modulating p38 phosphorylation and IL-8 gene expression following ICAM-1 engagement by HRV.

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“…11 challenged with ovalbumin is also enhanced, suggesting that other allergens, even without intrinsic proteolytic activity, may cause AHR by increasing the ability of the ASM to generate force. Finally, rhinovirus (specifically serotype 16, RV16), the virus primarily responsible for common colds and asthma exacerbation, and the virus mimitic polyinosinic:polycytidylic acid [13][14][15] were shown to potentiate ASM force development.…”

Section: Opinionmentioning

confidence: 98%

Asthmatic airway hyperresponsiveness: the ants in the tree

Bossé

2012

Trends in Molecular Medicine

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Rhinovirus elicits proasthmatic changes in airway responsiveness independently of viral infection

Cited by 41 publications

References 28 publications

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Syk Is Downstream of Intercellular Adhesion Molecule-1 and Mediates Human Rhinovirus Activation of p38 MAPK in Airway Epithelial Cells

Asthmatic airway hyperresponsiveness: the ants in the tree

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