Báo cáo y học: "Cytosolic phospholipase A2α mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR -/- mice"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: "Cytosolic phospholipase A2α mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR -/- mice. | Wu et al. Respiratory Research 2010 11 49 http content 11 1 49 RESPIRATORY RESEARCH RESEARCH Open Access Cytosolic phospholipase A2a mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR - - mice Yong-Zheng Wu 1 2 Mohammad Abolhassani3 Mario Ollero4 Fariel Dif1 2 Naonori Uozumi5 Micheline Lagranderie3 Takao Shimizu5 Michel Chignard1 2 and LhousseineTouqui 1 2 Abstract Background Lungs of cystic fibrosis CF patients are chronically infected with Pseudomonas aeruginosa. Increased airway constriction has been reported in CF patients but underplaying mechanisms have not been elucidated. Aim to examine the effect of P aeruginosa LPS on airway constriction in CF mice and the implication in this process of cytosolic phospholipase A2a cPLA2a an enzyme involved in arachidonic acid AA release. Methods Mice were instilled intra-nasally with LPS. Airway constriction was assessed using barometric plethysmograph. MIP-2 prostaglandin E2 PGE2 leukotrienes and AA concentrations were measured in BALF using standard kits and gas chromatography. Results LPS induced enhanced airway constriction and AA release in BALF of CF compared to littermate mice. This was accompanied by increased levels of PGE2 but not those of leukotrienes. However airway neutrophil influx and MIP-2 production remained similar in both mouse strains. The cPLA2a inhibitor arachidonyl trifluoro-methyl-ketone ATK but not aspirin which inhibit PGE2 synthesis reduced LPS-induced airway constriction. LPS induced lower airway constriction and PGE2 production in cPLA2a - - mice compared to corresponding littermates. Neither aspirin nor ATK interfered with LPS-induced airway neutrophil influx or MIP-2 production. Conclusions CF mice develop enhanced airway constriction through a cPLA2a-dependent mechanism. Airway inflammation is dissociated from airway constriction in this model. cPLA2a may represent a suitable target for therapeutic intervention in CF. Attenuation of airway .

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