Interaction of cigarette smoke and house dust mite allergens on inflammatory mediator release from primary cultures of human bronchial epithelial cells

Abstract

Several studies have shown that exposure to cigarette smoke and/or house dust mite (HDM) can lead to increased airway inflammation in susceptible individuals. The underlying mechanisms, however, are not defined. To investigate the interaction between cigarette smoke and HDM allergen on mediator release from primary cultures of human bronchial epithelial cells. Confluent human bronchial epithelial cell cultures were exposed to cigarette smoke in the absence or presence of HDM allergen and investigated for the release of IL-8, IL-1beta, and sICAM-1. Damage to the epithelial cells themselves was assessed by release of 51Cr. On separate occasions, we investigated the effect of PTL11028, a highly potent and selective Der p1 inhibitor, on HDM allergen-induced release of IL-8, following activation of HDM allergen by incubation with cysteine. The effect of cigarette smoke exposure on the stability of these released mediators in prepared solutions in the absence/presence of reduced glutathione was also studied. Both HDM allergens and short-term (20 min) cigarette smoke exposure led to a significantly increased release of IL-8, IL-1beta and sICAM-1 from the epithelial cell cultures. Longer exposure (1-6 h) to cigarette smoke led to a dramatic decrease in the amount of these mediators detected in the culture medium. Whilst incubation of epithelial cultures with HDM allergen did not cause any significant change in the release of 51Cr from pre-loaded cells, cigarette smoke on its own led to a marked, exposure and incubation-time dependent increase in the release of 51Cr. Incubation with HDM allergen led to a significant, dose and time-dependent increase in the release of IL-8, which was further enhanced when the allergen extract was pre-activated with cysteine. This effect was completely abrogated by PTL11028, a novel Der p1 inhibitor. Prepared solutions of various concentrations of IL-8, IL-1beta and sICAM-1 exposed to cigarette smoke demonstrated a dramatic exposure time-dependent decrease in the detectable amount of these mediators, an effect which was abrogated by GSH. HDM-induced airway inflammation may include Der p-mediated release of inflammatory mediators from epithelial cells. Additionally, short-term cigarette smoke exposure may induce airway inflammation by release of inflammatory mediators from these cells, an effect which may be potentiated by Der p allergens. Longer term cigarette smoke exposure may cause damage to epithelial cells and changes in the structure of inflammatory mediators.

Short cigarette smoke exposure facilitates sensitisation and asthma development in mice

“…In line with our observation, RUSZNAK et al [33] found increased inflammatory mediator release from primary in vitro cultures of human bronchial epithelial cells, after exposure to cigarette smoke and Der p allergens. BLACQUIÈ RE et al [34] examined the effect of maternal smoking during pregnancy.…”

Nicotine Induces the Production of IL-1� and IL-8 via the a7 nAChR/NF-κB Pathway in Human Periodontal Ligament Cells: anin VitroStudy

“…Additionally, Dongari-Bagtzoglou et al [29] reported that IL-8 expression is significantly higher in PDL cells from periodontitis patients than in PDL cells from healthy controls, and the level of IL-8 is negatively related to the periodontal treatment [14]. It has also been reported that tobacco smoke could up-regulate pro-inflammatory cytokines such as IL-8 in macrophages [30] as well as bronchial [31] and alveolar [32] epithelial cells. In nicotine-stimulated neutrophils, IL-8 expression was shown to be entirely dependent on NF-κB activation, as indicated by abrogation of IL-8 production in the presence of the NF-κB inhibitor, dexamethasone [33,34].…”

Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-κB activation in normal human bronchial epithelial cells

“…Studies show that short-term cigarette smoke exposure results in an enhanced release of IL-8, IL-1b and sICAM-1 in epithelial cell cultures (Rusznak et al, 2001). iNOS, expressed by both macrophages and epithelial cells during inflammation, plays an important role in inflammatory reactions via the production of nitric oxide.…”