p38 Inhibition Ameliorates Inspiratory Resistive Breathing-Induced Pulmonary Inflammation
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 < 0.001, respectively). Increased lung injury score was detected at 6 h IRB. SB203580 administration blocked the increase of neutrophils and macrophages at 6 h IRB (p = 0.01 and p = 0.005 to 6 h IRB) but not the increase in BAL protein and elasticity. TNF-α, MIP-2α, and injury score at 6 h IRB returned to control. p38 activation contributes to IRB-induced pulmonary inflammation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
|---|---|
| Enthalten in: |
Inflammation - 41(2018), 5 vom: 04. Okt., Seite 1873-1887 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Toumpanakis, Dimitrios [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.01.2019 Date Revised 09.01.2019 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1007/s10753-018-0831-6 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM286172631 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM286172631 | ||
| 003 | DE-627 | ||
| 005 | 20231225051055.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s10753-018-0831-6 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0953.xml |
| 035 | |a (DE-627)NLM286172631 | ||
| 035 | |a (NLM)29974374 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Toumpanakis, Dimitrios |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a p38 Inhibition Ameliorates Inspiratory Resistive Breathing-Induced Pulmonary Inflammation |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.01.2019 | ||
| 500 | |a Date Revised 09.01.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 < 0.001, respectively). Increased lung injury score was detected at 6 h IRB. SB203580 administration blocked the increase of neutrophils and macrophages at 6 h IRB (p = 0.01 and p = 0.005 to 6 h IRB) but not the increase in BAL protein and elasticity. TNF-α, MIP-2α, and injury score at 6 h IRB returned to control. p38 activation contributes to IRB-induced pulmonary inflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a lung | |
| 650 | 4 | |a p38 | |
| 650 | 4 | |a resistive breathing | |
| 650 | 7 | |a Chemokine CXCL2 |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a p38 Mitogen-Activated Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a SB 203580 |2 NLM | |
| 650 | 7 | |a OU13V1EYWQ |2 NLM | |
| 700 | 1 | |a Vassilakopoulou, Vyronia |e verfasserin |4 aut | |
| 700 | 1 | |a Mizi, Eleftheria |e verfasserin |4 aut | |
| 700 | 1 | |a Chatzianastasiou, Athanasia |e verfasserin |4 aut | |
| 700 | 1 | |a Loverdos, Konstantinos |e verfasserin |4 aut | |
| 700 | 1 | |a Vraila, Ioanna |e verfasserin |4 aut | |
| 700 | 1 | |a Perlikos, Fotis |e verfasserin |4 aut | |
| 700 | 1 | |a Tsoukalas, Dionysios |e verfasserin |4 aut | |
| 700 | 1 | |a Giannakopoulou, Charoula-Eleni |e verfasserin |4 aut | |
| 700 | 1 | |a Sotiriou, Adamantia |e verfasserin |4 aut | |
| 700 | 1 | |a Dettoraki, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Karavana, Vassiliki |e verfasserin |4 aut | |
| 700 | 1 | |a Vassilakopoulos, Theodoros |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Inflammation |d 1975 |g 41(2018), 5 vom: 04. Okt., Seite 1873-1887 |w (DE-627)NLM000293016 |x 1573-2576 |7 nnns |
| 773 | 1 | 8 | |g volume:41 |g year:2018 |g number:5 |g day:04 |g month:10 |g pages:1873-1887 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s10753-018-0831-6 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 41 |j 2018 |e 5 |b 04 |c 10 |h 1873-1887 | ||