Stretch induces a growth factor in alveolar cells via protein kinase.

Positive-pressure mechanical ventilation can injure the lung, causing edema and alveolar inflammation in a complication termed ventilator-induced lung injury (VILI). Cytokines such as interleukin-8 (IL-8) reportedly are important in this inflammatory response. On the other hand, hepatocyte growth factor (HGF) promotes regeneration of the lung, and delays pulmonary fibrosis. We postulated that cyclic stretch upregulates production and release of both of mediators. Human alveolar epithelial cells (A549) cultured on a silicoelastic membrane were tested for mRNA expression and release of IL-8 and HGF after cyclic stretch in vitro. Stretch induced mRNA expression and release of these mediators. The signaling pathway from cyclic stretch to release of IL-8 and HGF appeared to involve protein kinase C in the signal transduction pathway.

[1]  D. Mitchell,et al.  Platelet-derived growth factor-beta mRNA in human alveolar macrophages in vivo in asthma. , 1994, The European respiratory journal.

[2]  D. Mercola,et al.  The JUN Kinase/Stress-activated Protein Kinase Pathway Is Required for Epidermal Growth Factor Stimulation of Growth of Human A549 Lung Carcinoma Cells* , 1997, The Journal of Biological Chemistry.

[3]  K. Matsumoto,et al.  Hepatocyte growth factor may act as a pulmotrophic factor on lung regeneration after acute lung injury. , 1993, The Journal of biological chemistry.

[4]  S. Corroyer,et al.  Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease. , 1998, The European respiratory journal.

[5]  E. Perkett Role of growth factors in lung repair and diseases. , 1995, Current opinion in pediatrics.

[6]  K. Matsumoto,et al.  Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin. A morphologic study. , 1997, American journal of respiratory and critical care medicine.

[7]  Y. Ho,et al.  Involvement of Protein Kinase C-γ in IL-1β-Induced Cyclooxygenase-2 Expression in Human Pulmonary Epithelial Cells , 2000 .

[8]  M. Sporn,et al.  Differential regulation of the expression of transforming growth factor‐βs 1 and 2 by retinoic acid, epidermal growth factor, and dexamethasone in NRK‐49F and A549 cells , 1991, Journal of cellular physiology.

[9]  O. Potapova,et al.  The Jun Kinase 2 Isoform Is Preferentially Required for Epidermal Growth Factor-Induced Transformation of Human A549 Lung Carcinoma Cells , 1999, Molecular and Cellular Biology.

[10]  J. Chevrolet,et al.  Activation of human macrophages by mechanical ventilation in vitro. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[11]  T. LeVan,et al.  Glucocorticoid regulation of GM-CSF: evidence for transcriptional mechanisms in airway epithelial cells. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[12]  M. Takeya,et al.  Histopathologic pulmonary changes from mechanical ventilation at high peak airway pressures. , 1991, The American review of respiratory disease.

[13]  W. Seeger,et al.  Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. , 1998, The European respiratory journal.

[14]  Yoram Vodovotz,et al.  Regulation of transforming growth factor b1 by nitric oxide , 1999 .

[15]  R. W. Padgett,et al.  Genetic and biochemical analysis of TGFβ signal transduction , 1997 .

[16]  S. Thorgeirsson,et al.  Inhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Zhou Songyang,et al.  Determination of the Specific Substrate Sequence Motifs of Protein Kinase C Isozymes* , 1997, The Journal of Biological Chemistry.

[18]  A. Matsumori,et al.  Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[19]  Defining protective responses to pathogens: cytokine profiles in leprosy lesions. , 1991, Science.

[20]  S. Wilson,et al.  EGF, EGF receptor, basic FGF, TGF beta-1, and IL-1 alpha mRNA in human corneal epithelial cells and stromal fibroblasts. , 1992, Investigative ophthalmology & visual science.

[21]  H. Ploegh,et al.  A myristoylated pseudosubstrate peptide, a novel protein kinase C inhibitor. , 1993, The Journal of biological chemistry.