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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Asthma, Bronchial Hyperreactivity, Bronchoalveolar Lavage Fluid, Bronchoconstrictor Agents, Cytosol, Disease Models, Animal, Enzyme Activation, Histamine, Inflammation, Leukotriene B4, Male, Methacholine Chloride, Mice, Mice, Inbred BALB C, Mice, Knockout, Phospholipases A, Platelet Activating Factor, Pulmonary Eosinophilia, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha.
user
Does tNF-alpha induce the late-phase airway hyperresponsiveness and airway inflammation through cytosolic phospholipase A ( 2 ) activation? Context: Late-phase airway hyperresponsiveness (AHR) in asthma is considered the event leading to persistent inflammation in the lungs, but the molecular mechanisms involved in this process are poorly understood. To examine the role of TNF-alpha in the development of a late AHR and airway inflammation in asthma. We established a murine model of asthma with not only biphasic AHR to methacholine but also airway eosinophilia. The effect of TNF-alpha blockade was determined by using anti-TNF-alpha antibody and TNF-alpha knockout mice. Cytosolic phospholipase A(2) (cPLA(2)) mRNA expression and activity were assessed by using RT-PCR and 1-stearoyl-2-[1-(14)C] arachidonyl-sn-glycero-3-phosphocholine as the substrate, respectively. TNF-alpha blockade resulted in significant inhibition of the late AHR without affecting the early AHR, and reduction in airway eosinophilia and inflammation. cPLA(2) activity was increased in asthmatic lungs in a TNF-alpha-dependent way, and cPLA(2) inhibitor blocked late AHR and airway eosinophilia. TNF-alpha also stimulated the synthesis of cPLA(2) metabolites such as leukotriene B(4) and platelet-activating factor in the airway. Specific inhibitors of cPLA(2) metabolites inhibited the late AHR and airway eosinophilia.
assistant
TNF-alpha is the proximal key cytokine capable of developing late-phase AHR and subsequent airway inflammation through expression/activation of cPLA(2). Final Decision: yes