The Editors' choiceInduction of B7-H1 and B7-DC expression on airway epithelial cells by the Toll-like receptor 3 agonist double-stranded RNA and human rhinovirus infection: In vivo and in vitro studies
Section snippets
Rationale
To test the hypothesis that mucosal inflammation triggered by viral dsRNA might regulate B7 homolog expression, we examined the effect of synthetic dsRNA and anti-inflammatory glucocorticoid on B7 homolog expression in the immortalized BEAS2B airway epithelial cell line. Next we examined the ability of dsRNA to induce B7 homolog expression in cultured human primary bronchial epithelial cells (PBECs). Because HRV-16 is known to be a key trigger of exacerbations of CRS and asthma, we examined
Effect of dsRNA on B7 homolog expression in BEAS2B cells
The data in Fig 1 (upper panel) show that 24-hour exposure to dsRNA increased cell-surface expression of B7-H1 and B7-DC but not B7-H2 or B7-H3 in BEAS2B cells. mRNA analysis by means of real-time PCR supported these findings in that both B7-H1 and B7-DC mRNA levels were selectively induced in response to 24-hour exposure to dsRNA (Fig 1, lower panel). In contrast, dsRNA and fluticasone had little or no effect on levels of cell-surface expression and mRNA expression of B7-H2 and B7-H3. The
Discussion
Interactions between T cells and epithelial cells are thought to be important in the pathogenesis of asthma and CRS. Products of both TH1- and TH2-activated T cells are known to stimulate proinflammatory cytokine and chemokine production in epithelial cells. IL-4 and IL-13 secreted from TH2-activated T cells are known to stimulate signal transducer and activator of transcription 6–dependent secretion of eotaxin and other CC chemokines in epithelial cells.27, 28 Additionally, IL-1 and TNF-α are
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2014, Respiratory InvestigationCitation Excerpt :B7-H1 acts as a co-inhibitory molecule, and the upregulation of B7-H1 causes cytotoxic T lymphocyte (CTL) dysfunction, which subsequently impairs virus eradication [55,56]. Human airway epithelial cells constitutively expresses a low level of B7-H1, and poly-IC stimulation upregulates the expression of B7-H1 [57,58]. Given the high expression of PD-1 on CTLs, dsRNA-induced upregulation of B7-H1 might prevent the infected epithelial cells from being attacked by CTLs, thereby facilitating the spread of a virus to the neighboring cells (Fig. 3).
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2013, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Because exogenous IFN-β induced IL-13Rα2 expression, we hypothesized that the endogenous innate antiviral response would also induce IL-13Rα2 expression. Therefore we challenged fibroblasts with Poly (I:C), a synthetic dsRNA that is frequently used to mimic the replicative intermediate of single-stranded RNA viruses, such as rhinovirus.39-41 As shown in Fig 2, there was a significant induction of IL-13Rα2 mRNA and protein in presence of Poly (I:C) or IFN-β.
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2012, Microbes and InfectionCitation Excerpt :In vitro exposure of primary respiratory epithelial cells to HRV-16 resulted in induction of cell-surface expression of PD-L1 and PD-L2 [62]. Nasal scrapings taken at the time of peak symptom scores (3 days) after infection of 6 human subjects with HRV-16 displayed selective induction of levels of mRNA for PD-L1 and PD-L2 [62]. Our group, too, reported that in vitro RSV infection strongly up-regulates PD-L1 levels on epithelial cells [55,60].
Drug carrier nanoparticles that penetrate human chronic rhinosinusitis mucus
2011, BiomaterialsCitation Excerpt :Interesting, the same trend for the speeds of 100–500 nm PS-PEG particles in CRSM (200 nm > 100 nm > 500 nm) was also observed with CFS, although the absolute speeds of PS-PEG particles in CRSM are faster than those in CFS, suggesting that CRSM may pose an overall less tenacious diffusional barrier than CFS [16]. The similar barrier properties of CRSM and CFS may be attributed to the similar pathogenesis of the two diseases, in which the formation of an increasingly viscoelastic mucus gel is exacerbated by pathogenic infections and chronic inflammation [4,39]. Indeed, CRS occurs extremely frequently in CF patients, and carriers of a single CF mutation have a higher prevalence of CRS than the general population, suggesting the potential genetic linkage between the two diseases may have led to similarities in their nanoscale barrier properties [40,41].
Supported by National Institutes of Health grants (AI57400, M01-RR-02719, HL068546, and HL078860) and Flight Attendant Medical Research Institute.
Disclosure of potential conflict of interest: D. Proud has received research support from AstraZeneca. The rest of the authors have declared that they have no conflict of interest.