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Effect of pulmonary surfactant on innate immune responses in influenza virus infected human airway epithelial cells

Bulek, Anna Marta 2008. Effect of pulmonary surfactant on innate immune responses in influenza virus infected human airway epithelial cells. PhD Thesis, Cardiff University.

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Abstract

Overwhelming inflammatory responses leading to neutrophil invasion are hypothesised to be the main cause of mortality in influenza virus induced acute respiratory distress syndrome (ARDS). Previously, pulmonary surfactant has been shown to modulate inflammatory responses to bacterial agents. The aim of the present study was to investigate the effect of pulmonary surfactant on innate immune responses in an in vitro model of influenza virus infected human airway epithelial cells. Human lung type II alveolar epithelial cells A549 and BEAS-2B human bronchial epithelial cells were infected with influenza A virus H1N1 strains A/Swine/1976/31, A/WSN/33 and A/PR/8/34. Poly I:C, Escherichia coli Ol 11 :B4 LPS and measles virus strain Edmonston were used as cytokine stimulation controls. The effect of pulmonary surfactant was compared to that of dexamethasone. This in vitro study showed that physiological concentrations (up to 500 ug/ml) of clinically approved SP-A and SP-D depleted surfactant preparations (i) were non-toxic in BEAS-2B cells, (ii) had no effect on influenza virus infectivity, and (iii) reduced influenza virus induced cytokine production comparable to dexamethasone. Porcine Curosurf* significantly inhibited IL-8 and RANTES production in A/WSN/33 infected cells, by 30 and 35% respectively (p<0.05). Bovine Survanta* had a less pronounced effect. In luciferase reporter assays pulmonary surfactant, in contrast to dexamethasone, non-specifically inhibited both TLR3/RIG-I mediated NF-kappaB promoter activation and IFN-beta promoter activation. Our results indicate that SP-A and SP-D depleted surfactant preparations attenuate pro-inflammatory responses in influenza A virus infected human airway epithelial cells, but inhibitory effects on IFN-beta promoter activity were also observed. This suggests that pulmonary surfactant may be of clinical benefit in reducing pro-inflammatory responses in virus induced ARDS, however, a weakening of IFN-beta mediated anti-viral responses can not be excluded.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR355 Virology
ISBN: 9781303183270
Date of First Compliant Deposit: 30 March 2016
Last Modified: 09 Jan 2018 22:16
URI: http://orca-mwe.cf.ac.uk/id/eprint/55755

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