Role of the JNK pathway on the expression of inflammatory factors in alveolar macrophages under mechanical ventilation.

Abstract

The aim of this study was to investigate the regulatory role of the c-JUN N-terminal kinase (JNK) pathway on interleukin (IL)-8 and tumor necrosis factor (TNF)-α expression in alveolar macrophages (AMs) of injured lung. Lung injury was induced in the New Zealand white rabbit by applying continuous mechanical ventilation with or without inhibitor of JNK (SP600125), p38 (SB203580), or ERK (PD98059). Non-ventilated rabbits (controls) were compared with the different ventilation-days groups, and untreated rabbits ventilated for 3 days (controls) were compared with the different inhibitor groups. We found that mechanical ventilation caused significant decreases in partial pressures of carbon dioxide (pCO2) and oxygen (pO2) of untreated rabbits (all times, P<0.05), but the inhibitor-treated groups showed no change in either blood-gas indicator (all times, P>0.05). Mechanical ventilation caused time-dependent increases in mRNA and protein levels of TNF-α and IL-8 in AMs and in serum of untreated rabbits, with the peak levels occurring at day 3 of ventilation. The SP600125-treated group showed significantly decreased TNF-α expression, but no significant change in IL-8 expression. Neither the SB203580- nor PD98059-treated groups showed any significant change in TNF-α or IL-8 expression. MAPKs' inhibitors could reduce mechanical ventilation-induced inflammation, and SP600125 produced the most robust decrease in inflammation. Mechanical ventilation-induced lung injury stimulates IL-8 and TNF-α expression in rabbit AMs in a time-dependent manner. The JNK pathway plays an important role in mechanical ventilation-stimulated TNF-α expression in AMs, but the injury-stimulated IL-8 expression may be regulated by other signaling pathways.

• Authors: Jin Tong, Xiang-Dong Zhou, Victor P Kolosov, Juliy M Perelman
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 17 Issue 3 Pg. 821-7 (Nov 2013) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24070709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Interleukin-8
• Tumor Necrosis Factor-alpha
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Interleukin-8 (genetics, metabolism)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Lung (pathology)
• Macrophages, Alveolar (metabolism)
• Male
• Pneumonia (metabolism, pathology)
• Rabbits
• Respiration, Artificial
• Tumor Necrosis Factor-alpha (genetics, metabolism)