Cigarette smoke extract modulates IL-8 release from cystic fibrosis bronchial epithelial cell lines

Williams, M.T., Ennis, M. and Elborn, J.S. (2008) Cigarette smoke extract modulates IL-8 release from cystic fibrosis bronchial epithelial cell lines. In: nd Annual North American Cystic Fibrosis Conference, Orlando, FL,USA, 23-25 Oct 2008, pp. 287-288. (doi: 10.1002/ppul.20939)

Abstract

Chronic lung disease associated with persistent infection and inflammation is the cause of death of most CF patients. The airways contain excess neutrophils as well as increased levels of pro-inflammatory cytokines. Bronchial epithelial cells play a crucial role in the establishment and continuation of this inflammatory response as they release large amounts of proinflammatory mediators e.g. IL-8 in response to inflammatory stimuli. Cigarette smoke can modulate the release of inflammatory cytokines. The aim of this study was therefore to compare the effects of cigarette smoke extract (CSE) on basal and induced IL-8 secretion from 2 bronchial epithelial cell lines (CFBE41o- and 16HBE14o-). Cells (gift from Dieter C. Gruenert, USF) were pretreated for 4 h with or without 5% CSE. They were then stimulated with LPS from P. aeruginosa (LPS-PA 50 + 100 µg/ml); cytomix 1 (TNF-α 10 ng/ml, IL-1β 5 ng/ml, LPS-PA 5 µg/ml) or cytomix 2 (TNF-α 10 ng/ml, IL-1β 10 ng/ml, IFN-γ 1000 U/ml). Culture supernatants were collected and IL-8 release measured using ELISA (Pelikine). Exposure to CSE significantly reduced the stimulated IL-8 release in all cases in the CFBE41o- cells (cytomix 1: 883.2±143.2 pg/ml, +CSE 575.2±185.4 pg/ml; cytomix 2 3646±520.1 pg/ml, +CSE 1780±304.9 pg/ml; LPS-PA 100 µg/ml 470.5±80.9 pg/ml, +CSE 281.7±64.9 pg/ml; all p<0.05). In contrast, IL-8 release from 16HBE14o- cells was only significantly inhibited basally and after stimulation with cytomix 2 (cytomix 2 1573±215.7 pg/ml, +CSE 1159±343.5 pg/ml; p<0.05). Furthermore, IL-8 release from CFBE41o- cells was significantly elevated basally and after stimulation with Cytomix 2 and LPS 50 µg/ml compared to 16HBE14o- cells. These data indicate that the response of the CF cell line to CSE differs from that of the normal cell line. CSE has recently been shown to inhibit TLR4 in A549 cells causing a reduction in both basal and LPS stimulated IL-8 release [1]. This would provide a rationale for reduced responses to cytomix 1 or LPS. Further studies will examine the effect of CSE on TLR4 in our cell lines. In contrast to the work of Kode et al. we observed an inhibition of basal IL-8 release in the 16HBE14o- cells [2]. They observed no effect in a variety of cell lines but an induction of IL-8 release in primary human small airway epithelial cells. We will investigate this further using primary nasal epithelial cell from control subjects and patients with CF. [1] MacRedmond RE et al. Respir Res. 2007; 8:84 [2] Kode A et al. Respir Res. 2006;7:132

• Item Type: Conference Proceedings
• Additional Information: Published in Pediatric Pulmonology, Volume 43, Issue S31, pages 202–462, 2008
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Williams, Dr Mark
• Authors: Williams, M.T., Ennis, M., and Elborn, J.S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Pediatric Pulmonology
• Publisher: John Wiley and Sons, Inc.
• ISSN: 8755-6863
• ISSN (Online): 1099-0496