title: Activations of mitogen-activated protein kinase and nuclear factor-kappaB by mechanical stretch result in ventilation-induced lung injury.
abstract: Mechanical ventilation is an important therapeutic technique for patients with respiratory failure. Nonetheless, it may cause or worsen lung injury. The specific triggers for cytokine release and the cellular origins of the inflammatory mediators in ventilation-induced lung injury (VILI) have yet to be defined. With the development of cytomechanics, we can study the lung cell response to mechanical strain. The initial step is mechanosensation, including stretch-activated ionchannels and the ECM-integrin-cytoskeleton pathway. Several intracellular signaling pathways then are activated and eventually result in increased transcription of specific genes. Mitogen-activated protein kinase cascade, nuclear factor(NF)-kappaB, PKC are all activated by mechanical stretch. But the mechanisms regulating lung stretch-induced cytokine production are still unclear. I hypotheses mechanical stretch initiate specific genes transcription, then the cytokines stimulate the cell again. This formed a positive feed back loop, which caused VILI. These studies may lead to the identification of new targets for therapeutic interventions and help to develop less aggressive ventilation strategies for patients with acute respiratory failure.
authors.affiliation: Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Dongfong Road 1630, Shanghai, PR China.
authors.forename: Qiao-ming
authors.initials: QM
authors.lastname: Ning
authors.forename: Xiang-rui
authors.initials: XR
authors.lastname: Wang
mesh_terms: D004789:Enzyme Activation; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D055370:Lung Injury; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011661:Pulmonary Stretch Receptors / Q000502:physiology*; D012121:Respiration, Artificial / Q000009:adverse effects*
chemical_list: D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases