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Expression and regulation of CCL 15 by human airway smooth muscle cells
Author(s) -
Joubert P.,
LajoieKadoch S.,
Wellemans V.,
Létuvé S.,
Tulic M. K.,
Halayko A. J.,
Hamid Q.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2011.03894.x
Subject(s) - chemokine , dexamethasone , chemistry , immunology , airway , asthma , immune system , chemotaxis , interleukin 8 , inflammation , tumor necrosis factor alpha , medicine , endocrinology , biochemistry , receptor , surgery
Summary Background Structural cells are an important reservoir of chemokines that coordinate the influx of various immune cells to the lungs of asthmatics. Airway smooth muscle cells ( ASMC ) are an important source of these chemokines. CCL 15 is a recently described chemo‐attractant for neutrophils, eosinophils, monocytes and lymphocytes. Objective To determine the production and the regulation of CCL 15 by ASMC and to investigate its production in asthmatic airways. Methods Human ASMC were obtained from main bronchial airway segments of patients with mild, moderate and severe asthma. To induce chemokine production, cells were incubated with IL ‐4, IL ‐13, TNF ‐α or IFN ‐γ in presence or absence of dexamethasone, mithramycin A ( SP ‐1 inhibitor) or the IKK ‐2 inhibitor, AS 602868. CCL 15 m RNA expression was evaluated by real‐time PCR . Immunoreactive CCL 15 was detected by immuno‐fluorescence and CCL 15 protein concentration in the supernatant was measured using ELISA . Results CCL 15 is constitutively expressed in human ASMC and is strongly up‐regulated by TNF ‐α. This up‐regulation is inhibited by dexamethasone, mithramycin A and AS 602868. TNF ‐α‐induced CCL 15 levels can be synergistically enhanced by the presence of IFN ‐γ, at both the transcriptional and translation level. This synergism is NF ‐κB‐dependent. Asthmatic biopsies demonstrated higher expression of CCL 15 compared with non‐asthmatic controls. Conclusion and Clinical Relevance Our results show that ASMC are a potent source of CCL 15 in the airways and may directly participate in the recruitment of inflammatory cells to asthmatic airways. Targeting the production of CCL 15 by ASMC might reduce the inflammatory response within the airways of asthmatic patients.