Stretch-induced IL-8 depends on c-Jun NH2-terminal and nuclear factor-kappaB-inducing kinases
| Autor: | Marcella M. Mascarenhas, Deborah A. Quinn, Bin Ouyang, Robina Matyal, Li-Fu Li, Thomas Force, Behrouz Jafari, Joseph V. Bonventre, Gabriel Choukroun |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Physiology MAP Kinase Signaling System medicine.medical_treatment Recombinant Fusion Proteins Respiratory Mucosa Cell Line Physiology (medical) Internal medicine medicine Humans Interleukin 8 Enzyme Inhibitors Phosphorylation Protein kinase A Cell Size Anthracenes Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Kinase c-jun Interleukin-8 JNK Mitogen-Activated Protein Kinases NF-kappa B Interleukin Cell Biology beta-Galactosidase Cell biology Pulmonary Alveoli Endocrinology Cytokine Mitogen-activated protein kinase biology.protein Stress Mechanical Mitogen-Activated Protein Kinases |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 285(2) |
| ISSN: | 1040-0605 |
| Popis: | Positive pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including interleukin (IL)-8. The mechanisms regulating lung stretch-induced cytokine production are unclear. We hypothesized that stretch-induced IL-8 production is dependent on the activation of the mitogen-activated protein kinases, c-Jun NH2-terminal kinases (JNK), p38, and/or extracellular signal-regulated kinase (ERK) 1/2. We exposed A549 cells, a type II-like alveolar epithelial cell line, to cyclic stretch at 20 cycles/min for 5 min–2 h. Cyclic stretch induced IL-8 protein production, IL-8 mRNA expression, and JNK activation, but only transient activation of p38 and ERK1/2. Inhibition of stretch-induced JNK activation by adenovirus-mediated gene transfer of stress-activated protein kinase (SEK-1), a dominant-negative mutant of SEK-1, the immediate upstream activator of the JNKs, and pharmacological JNK inhibitor II SP-600125 blocked IL-8 mRNA expression and attenuated IL-8 production. Inhibition of p38 and ERK1/2 did not affect stretch-induced IL-8 production. Stretch-induced activation NF-κB and activator protein (AP)-1 was blocked by NF-κB inhibitor and JNK inhibitor, respectively. An NF-IL-6 site was not essential for cyclic stretch-induced IL-8 promoter activity. Stretch also induced NF-κB-inducing kinase (NIK) activation, and inhibition of NF-κB attenuated IL-8 mRNA expression and IL-8 production. We conclude that stretch-induced transcriptional regulation of IL-8 mRNA and IL-8 production was via activation of AP-1 and NF-κB and was dependent on JNK and NIK activation, respectively. |
| Databáze: | OpenAIRE |
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