Background Chronic obstructive pulmonary disease (COPD) is characterised by repeated viral or bacterial exacerbations which increase morbidity, mortality and accelerate lung function decline. Chronic bacterial colonisation, frequently recognised in stable COPD patients, may contribute to airway inflammation and promote disease progression. Cigarette smoke has previously been shown to alter responses to LPS via the TLR-4 receptor in cell lines. We hypothesised that cigarette smoke would suppress the innate immune responses of airway epithelial cells and macrophages to Haemophilus influenzae (HI) favouring persistence.
Methods Primary bronchial epithelial cells (PBEC) and macrophage-like cells (THP-1) were incubated with varying concentrations of cigarette smoke extract (CSE) before stimulation with whole cell lysates of HI prepared from clinical isolates. Cell viability was assessed by flow cytometry and PBEC proliferation was analysed using an XTT assay. Pro-inflammatory cytokine release (IL-8, TNFα, IL-1β) was assessed in PBEC and PMA-differentiated THP-1 cells by ELISA.
Results CSE concentrations ≤10% had no significant effect on PBEC or THP-1 cell viability, however CSE concentrations >5% inhibited PBEC proliferation (p<0.05, n=9). PBEC demonstrated increased release of IL-8 in response to treatment with 5% CSE and increasing doses of HI (n=3, p<0.05). Co-treatment with HI + CSE accentuated IL-8 release from PBEC even at CSE concentrations of 1–2.5% which had no effect alone (p<0.05, n=6). TNFα and IL-1β release from PBEC were below the detection limit of the ELISA. THP-1 cells increased the release of IL-8, TNF-α and IL-1β in response to treatment with HI (n=3, p<0.05) however CSE alone had no effect on cytokine production (n=3, p>0.05). Co-treatment of THP-1 cells with HI + CSE increased IL-8 release (61%), but reduced TNF-α (40%) and IL-1β (24%) release compared to treatment with HI alone (n=3, p<0.05).
Conclusions CSE alters epithelial cell and macrophage responses to bacterial pathogens by promoting release of the neutrophil chemokine IL-8 whilst at the same time suppressing TNFα and IL-1 β release. This dysregulation may promote continued neutrophil inflammation in the airway whilst insufficiently clearing pathogens and could be an important mechanism in COPD.
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