???? Facilitate Neutrophil Apoptosis And Attenuates Ovalbumin Plus Lipopolysaccharide Induced Neutrophilic Asthma

ObjectiveTo investigate whether ???? alleviates neutrophilic asthma with an emphasis on neutrophil apoptosis and airway smooth muscle cells ASMCs migration.MethodsThe effect of ???? on airway inflammation was evaluated in a murine model of neutrophilic asthma sensitized with ovalbumin and lipopolysaccharide.Bronchoalveolar lavage(BAL)and lung tissue were examined for inflammation and inflammatory mediator production.Airway hyper-responsiveness to aerosolized methacho line was measured.Human neutrophil apoptosis in response to ???? was investigated by cellular morphology,flow cytometry,and pharmacological caspase inhibition.The migration of ASMCs in response to HMGB1 was tested in vitro.Results(1)In vivo,???? administration attenuated airway inflammation with resolution of BALF and interstitial neutrophil numbers and TNF-? and IL-6 concentrations in the lung,and abolished airways hyper-responsiveness.(2)???? induced concentration-dependent neutrophil apoptosis in vitro.Induction of apoptosis was caspase dependent,as it was blocked by the pharmacological caspase inhibitor Q-VD-OPh and z-VAD-fmk and was associated with activation of both caspase-3 and caspase-8 activation.(3)???? alleviated HASMCs proliferation and migration by declining thephosphorylation of MAPK which was activated by High-mobility group box protein 1(HMGB1).Conclusions???? induces neutrophil apoptosis and attenuates airway remodeling,suggesting therapeutic potential for treating severe asthma in human.