title: Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels.
abstract: In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3(+) mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1 β , TNF- α , and/or IFN γ and treated with histamine (1-100  μ M) ± chlorpheniramine (H1R antagonist; 1  μ M) or ranitidine (H2R antagonist; 50  μ M) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50  μ M), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1 β /TNF- α -induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF- α and amplified IFN γ -induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Alkhouri
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Cha
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Tong
authors.affiliation: Discipline of Pharmacology and Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: L M
authors.initials: LM
authors.lastname: Moir
authors.affiliation: Discipline of Pharmacology and Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: C L
authors.initials: CL
authors.lastname: Armour
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Hughes