p38 Inhibition Ameliorates Inspiratory Resistive Breathing-Induced Pulmonary Inflammation
| Autor: | Konstantinos Loverdos, Vyronia Vassilakopoulou, Athanasia Chatzianastasiou, Dionysios Tsoukalas, Adamantia Sotiriou, Theodoros P. Vassilakopoulos, Vassiliki Karavana, Maria Dettoraki, Eleftheria Mizi, Fotis Perlikos, Dimitrios Toumpanakis, Ioanna Vraila, Charoula-Eleni Giannakopoulou |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Neutrophils Pyridines p38 mitogen-activated protein kinases education Immunology Chemokine CXCL2 Inflammation Lung injury p38 Mitogen-Activated Protein Kinases 03 medical and health sciences 0302 clinical medicine health services administration Internal medicine medicine Immunology and Allergy Animals Enzyme Inhibitors health care economics and organizations Lung medicine.diagnostic_test business.industry Tumor Necrosis Factor-alpha Pulmonary inflammation Macrophages Imidazoles Lung Injury Pneumonia respiratory system humanities Rheumatology Rats 030104 developmental biology Bronchoalveolar lavage medicine.anatomical_structure 030228 respiratory system Inhalation Anesthesia medicine.symptom business Airway Bronchoalveolar Lavage Fluid |
| Zdroj: | Inflammation. 41(5) |
| ISSN: | 1573-2576 |
| Popis: | Inspiratory resistive breathing (IRB), a hallmark of obstructive airway diseases, is associated with strenuous contractions of the inspiratory muscles and increased negative intrathoracic pressures that act as an injurious stimulus to the lung. We have shown that IRB induces pulmonary inflammation in healthy animals. p38 kinase is activated in the lung under stress. We hypothesized that p38 is activated during IRB and contributes to IRB-induced pulmonary inflammation. Anesthetized, tracheostomized rats breathed spontaneously through a two-way valve. Resistance was connected to the inspiratory port to provoke a peak tidal inspiratory pressure 50% of maximum. Following 3 and 6 h of IRB, respiratory system mechanics were measured and bronchoalveolar lavage (BAL) was performed. Phosphorylated p38, TNF-α, and MIP-2α were detected in lung tissue. Lung injury was estimated histologically. SB203580 (p38 inhibitor) was administered prior to IRB (1 mg kg−1). Six hours of IRB increased phosphorylated p38 in the lung, compared with quietly breathing controls (p = 0.001). Six hours of IRB increased the numbers of macrophages and neutrophils (p = 0.01 and p = 0.005) in BAL fluid. BAL protein levels and lung elasticity increased after both 3 and 6 h IRB. TNF-α and MIP-2α increased after 6 h of IRB (p = 0.01 and p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink