Abstract
Human rhinovirus (HRV) infections induce epithelial cell production of chemokines that may contribute to the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. Cigarette smoking is the predominant risk factor for the development of COPD and also aggravates asthma symptoms. We examined whether cigarette smoke extract (CSE) modulates viral inflammation by altering the profile of HRV-induced epithelial chemokine production. Purified HRV-16, and CSE were used to examine the effects on CXC chemokine ligand (CXCL)8 and CXCL10 production from both primary human bronchial epithelial cells and the BEAS-2B epithelial cell line. Both CSE and HRV-16 induced CXCL8 production and, when used in combination, induced at least an additive production of CXCL8 compared with either stimulus alone. In contrast, CSE did not induce CXCL10 and markedly inhibited HRV-16-induced CXCL10 production. Inhibition of HRV-16-induced CXCL10 by CSE was mediated, at least in part, via transcriptional regulation. The increased CXCL8 production seen with the combination of CSE and HRV-16 was not due to transcriptional regulation but was associated with CXCL8 mRNA stabilisation. Thus, CSE differentially modulates HRV-16-induced chemokine production from human airway epithelial cells in a manner that might be expected to alter inflammatory cell profiles.
Highlights
Purified Human rhinovirus (HRV)-16, and cigarette smoke extract (CSE) were used to examine the effects on CXC chemokine ligand (CXCL)8 and CXCL10 production from both primary human bronchial epithelial cells and the BEAS-2B epithelial cell line
It has been previously reported that CSE itself induces CXCL8 production from epithelial cells [21], our data are the first to show more than additive induction by the combination of CSE and HRV infection
CSE did not induce CXCL10 production from epithelial cells and strikingly inhibited HRV-induced CXCL10 production. These interactions were not unique for HRV type 16 (HRV-16), as CSE caused similar modulation of chemokine responses induced by the minor group serotype, HRV type 1A (HRV-1A)
Summary
Purified HRV-16, and CSE were used to examine the effects on CXC chemokine ligand (CXCL) and CXCL10 production from both primary human bronchial epithelial cells and the BEAS-2B epithelial cell line. Both CSE and HRV-16 induced CXCL8 production and, when used in combination, induced at least an additive production of CXCL8 compared with either stimulus alone. Epithelial cells infected with HRV produce numerous chemokines, cytokines and host defence molecules [2]. Several of these chemokines, including CXCL8 and CXCL10, are observed in increased amounts in airway secretions during in vivo HRV infections. CXCL10 is a chemoattractant for activated lymphocytes and natural killer cells that have been linked to host antiviral defences
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