Activation of the STAT pathway in acute lung injury
| Autor: | George Perides, Paul M. Hassoun, Michael L. Steer, Amy Simon, Satoe Takahashi, Brent H. Cochran, Liliana M. Rozo, Jhung W. Jhung, Charles Kuhn, Barry L. Fanburg, Mariano Severgnini, Robert J. Homer |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
Male STAT3 Transcription Factor Pulmonary and Respiratory Medicine Physiology medicine.medical_treatment Respiratory Mucosa Lung injury stat Mice Proto-Oncogene Proteins Physiology (medical) medicine Animals STAT3 Lung Transcription factor Cells Cultured Mice Inbred BALB C Respiratory Distress Syndrome biology Interleukin-6 Tumor Necrosis Factor-alpha business.industry JAK-STAT signaling pathway Cell Biology Janus Kinase 2 Protein-Tyrosine Kinases respiratory system respiratory tract diseases DNA-Binding Proteins Mice Inbred C57BL Disease Models Animal Kinetics src-Family Kinases Cytokine Liver Pancreatitis Acute Disease Immunology Trans-Activators biology.protein STAT protein Hydrochloric Acid Mitogen-Activated Protein Kinases business Oxidation-Reduction |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 286:L1282-L1292 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00349.2003 |
| Popis: | Acute lung injury (ALI) is a devastating clinical problem with a mortality as high as 60%. It is now appreciated that ALI represents a cytokine excess state that involves the microvasculature of multiple organs. The signal transducers and activators of transcription (STAT) family of transcription factors activate critical mediators of cytokine responses, but there is limited knowledge about their role in mediating ALI. In the present study, we demonstrate that the STAT transcription factors are activated rapidly in the lungs after intraperitoneal and intranasal LPS administration in mice. We also demonstrated that LPS activates both the STAT kinases, Src and JAK, in the lung with kinetics that are consistent with STAT activation. LPS treatment resulted in STAT3 activation throughout the resident lung cells, as well as in the recruited inflammatory cells. Whereas direct LPS treatment did not lead to STAT activation in cultured epithelial or endothelial cells, IL-6 activated STAT3 in both of these cell types. Furthermore, IL-6 was induced by LPS in serum and in the lung with kinetics consistent with STAT3 activation, suggesting that IL-6 may be one mechanism of STAT activation by LPS. In addition, STAT activation required reactive oxygen species, as the overexpression of catalase in mice prevented LPS-mediated STAT activation in the lung. STATs may be a common pathway for mediating ALI, regardless of the inciting factor, as STAT activation also occurred in both a gastric acid aspiration and acute pancreatitis model of ALI. Finally, STATs are activated in the lung long before signs of ALI are present, suggesting that the STAT transcription factors may play a role in initiating the inflammatory response seen in the lung. |
| Databáze: | OpenAIRE |
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