title: Cigarette smoke stimulates the production of chemokines in mast cells.
abstract: Chronic obstructive pulmonary disease is a major health problem and will become the third largest cause of death in the world by 2020. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular, cigarette smoke (CS), causes the progressive airflow limitation, in which macrophages and neutrophils are attracted by chemokines, leading to oxidative stress, emphysema, small airways fibrosis, and mucus hypersecretion. Smoking is also associated with an increase in mast cell numbers in bronchial mucosa. This study was conducted to determine the direct effects of CS on mast cell function, using murine bone marrow-derived mast cells (BMMC) as an in vitro model. BMMC were cultured from BALB/cBy mice for 3 weeks. Cells were treated with CS medium (CSM) for 30 min or 16 h. The effects of CSM on mast cell degranulation and chemokine production were measured. Moreover, we investigated the effect of CSM on IkappaB-alpha degradation and p38, Erk1/2, p65, and CREB expression by Western blotting. We found that CSM stimulated the release of chemokines in a noncytotoxic manner but did not induce mast cell degranulation. CSM induced phosphorylation of Erk1/2, p38, and CREB and increased translocation of p65 without degradation of IkappaB-alpha NF-kappaB in mast cells. The induction of chemokine production by CSM in mast cells could promote and prolong the inflammatory process. Our observations suggest that mast cells may contribute to the pathogenesis of emphysema through a direct effect of CS on the production of proinflammatory chemokines.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, Utrecht, The Netherlands. e.mortaz@uu.nl
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mortaz
authors.forename: Frank A
authors.initials: FA
authors.lastname: Redegeld
authors.forename: Hadi
authors.initials: H
authors.lastname: Sarir
authors.forename: Khalil
authors.initials: K
authors.lastname: Karimi
authors.forename: Danielle
authors.initials: D
authors.lastname: Raats
authors.forename: Frans P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D018925:Chemokines; D012906:Smoke; D048049:Extracellular Signal-Regulated MAP Kinases