Stretch induces cytokine release by alveolar epithelial cells in vitro

Vlahakis, Nicholas E.; Schroeder, Mark A.; Limper, Andrew H.; Hubmayr, Rolf D.

doi:10.1152/ajplung.1999.277.1.l167

Cited by 286 publications

(309 citation statements)

References 35 publications

Supporting

Mentioning

282

Contrasting

Unclassified

Order By: Relevance

“…By using in situ hybridization, FODA et al [32] showed activation of the extracellular matrix metalloprotein inducer (EMMPRIN), gelatinase A and gelatinase B, in alveolar macrophages, alveolar epithelial cells and endothelial cells from rats ventilated with 20 mL?kg -1 and no PEEP for 4 h [32]. In the present study, [33] and IL-8 from stretched alveolar epithelial cells [34]. Indirect evidence of the type II cells9 responsiveness to stretch was already provided almost 20 yrs ago, when it was shown that even one single deep breath is sufficient to release pulmonary surfactant [35].…”

Section: Discussionmentioning

confidence: 48%

Ventilation-induced activation of the mitogen-activated protein kinase pathway

Uhlig

Haitsma²,

Goldmann³

et al. 2002

European Respiratory Journal

View full text Add to dashboard Cite

Mechanical ventilation of patients can be a life-saving treatment, but also imposes additional stress on the lung. Mitogen-activated protein kinases (MAPK) represent a family of protein kinases that become phosphorylated and activated by many different forms of stress.Using Western blot analysis, the present study analysed the effects of high distending pressure ventilation on the activation of the MAPK extracellular signal-related kinases (ERK)-1/2, c-Jun amino-terminal kinases (JNK) and p38 kinase, and on the MAPKactivated transcription factors c-Jun, ETS-like protein (Elk)-1 and activating transcription factor (ATF)-2.In adult rats, ventilation with high pressure (45/10 peak inspiratory pressure/positive end-expiratory pressure in cmH 2 O) for 30 or 60 min did not affect arterial oxygenation, but resulted in enhanced phosphorylation of ERK-1/2, JNK, c-Jun, Elk-1 and ATF-2 compared to normally ventilated (13/3) rats. The activation of ERK-1/2 and JNK was located to cells resembling alveolar type II cells. In addition, high pressure ventilation enhanced phosphorylation of the inhibitor of nuclear factor (NF)-kB and nuclear translocation of the transcription factor NF-kB. In isolated perfused mouse lungs, the MAPK/ERK kinase inhibitor U0126 prevented ventilation-induced activation of ERK-1/2 and Elk-1, but had no effect on ventilation-induced cytokine release.The present authors conclude that mechanical ventilation triggers specific signalling pathways, such as the mitogen-activated protein kinase and the nuclear factor-kB pathways, which may contribute to pulmonary inflammation and proliferation. Eur Respir J 2002; 20: 946-956.

show abstract

Section: Discussionmentioning

confidence: 48%

Ventilation-induced activation of the mitogen-activated protein kinase pathway

Uhlig

Haitsma²,

Goldmann³

et al. 2002

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…Additionally, inhaled CO also reduced BALF macrophage numbers at 2 hours. TNF-␣ is a well known and well investigated cytokine that has a proinflammatory effect in in vivo and in vitro models (10,30), and IL-10 has antiinflammatory activity in LPS-induced inflammation (31). It is interesting to note that CO did not affect the BALF protein levels, suggesting that CO exerts negligible effects on pulmonary permeability.…”

Section: Discussionmentioning

confidence: 99%

Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury

Dolinay

Szilasi

Liu

et al. 2004

Am J Respir Crit Care Med

138

127

View full text Add to dashboard Cite

Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality in intensive care units. The stress-inducible gene product, heme oxygenase-1, and carbon monoxide (CO), a major byproduct of heme oxygenase catalysis of heme, have been shown to confer potent antiinflammatory effects in models of tissue and cellular injury. In this study, we observed increased expression of heme oxygenase-1 mRNA and protein in a rat model of VILI. To assess the physiologic function of heme oxygenase-1 induction in VILI, we determined whether low concentration of inhaled CO could serve to protect the lung against VILI. Low concentration of inhaled CO significantly reduced tumor necrosis factor-␣ levels and total cell count in lavage fluid, while simultaneously elevating levels of antiinflammatory interleukin-10 levels. To better characterize the mechanism of CO-mediated antiinflammatory effects, we examined key signaling pathways, which may mediate CO-induced antiinflammatory effects. We demonstrate that inhaled CO exerts antiinflammatory effects in VILI via the p38 mitogen-activated protein kinase pathway but independent of activator protein-1 and nuclear factor-B pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI. Keywords: cytokines; heme oxygenase-1; p38 MAPKAccording to an international study, an average of 39% of intensive care unit patients requires mechanical ventilation worldwide (1). Many of these patients develop ventilator-induced lung injury (VILI) (2). Eventually VILI contributes to acute respiratory distress syndrome (ARDS), which has a 40 to 50% mortality rate (3). Although clinical trials showed that ARDS/VILI-related mortality could be attenuated with lower tidal volume ventilation, positive end-expiratory pressure (PEEP) ventilation, and more recently, with recruitment maneuver combined with protective ventilation strategy, the syndrome remains a major problem in intensive care units (3)(4)(5).It is established that mechanical ventilators that apply high volumes and pressures can lead to increased alveolar-capillary permeability (6). This loss of compartmentalization results in increased fluid influx to the alveoli from the capillaries, causing pulmonary edema. The injured or ruptured cells attract neutrophil leukocytes and activate alveolar macrophages, causing inflammation in the lung (6). Tremblay and colleagues have suggested that ventilation can provoke an inflammatory response in the distal airway and alveolar cells (7), manifested by increased production of proinflammatory cytokines. It is speculated that the released proinflammatory cytokines could enter the circulation causing inflammation in other systemic organs. In addition, the previously diseased or injured lungs are more susceptible to subsequent mechanical ventilation, releasing more proinflammatory cytokines than healthy lungs, perhaps reflecting the cumulative effects of multiple injuries (8, 9). Lipopolysaccharide (LPS), acid aspiration, and cecal ligation/perforation-induced sep...

show abstract

“…Neutrophil recruitment to the lungs might be a critical step in the pathogenesis of ventilator-induced lung injury (18,33). The likely cellular sources of IL-8 in the lung are the respiratory epithelium and alveolar macrophages (16,42).…”

mentioning

confidence: 99%