Dual Effects of p38 MAPK on TNF-Dependent Bronchoconstriction and TNF-Independent Neutrophil Recruitment in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

Schnyder‐Candrian, Silvia; Quesniaux, Valérie; Padova, Franco Di; Maillet, Isabelle; Noulin, Nicolas; Couillin, Isabelle; Moser, René; Erard, François; Vargäftig, B. Boris; Ryffel, Bernhard; Schnyder, Bruno

doi:10.4049/jimmunol.175.1.262

Cited by 93 publications

(74 citation statements)

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“…First, many of the protein pathways were redundant. For example, the p38 MAPK pathway has been implicated in the development of the exaggerated inflammation that is seen in ARDS (20). The network analysis showed that p38 MAPK may trigger part of its biological effect by increasing the expression of TNF-a, among other proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies showed that TNF-a, IL-1b, IL-6, and LBP are present in the BALF of patients with ARDS and contribute to the pro-inflammatory environment (16)(17)(18)(19)(20). In addition, p38 MAPK has also been shown to regulate key physiologic responses, including neutrophil recruitment and clearance of edema fluid, during the development of lung injury (20)(21)(22)(23). The proteins that were added into the network were predominantly cytokines, intracellular signaling proteins, and transcription factors that exist in extremely low concentrations in the BALF.…”

Section: Discussionmentioning

confidence: 99%

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Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Chang¹,

Hayashi²,

Gharib³

et al. 2008

Am J Respir Crit Care Med

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Rationale: Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. Objectives: The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Methods: Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n 5 7), 3 (n 5 8), and 7 (n 5 5) of ARDS were compared with findings in normal volunteers (n 5 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. Measurements and Main Results: An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Conclusions: Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Chang¹,

Hayashi²,

Gharib³

et al. 2008

Am J Respir Crit Care Med

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“…As mock control, WT mice were administered with saline. The airway function was evaluated by whole-body plethysmography [6]. Unrestrained conscious mice were placed in plethysmography chambers (EMKA Technologies, France), and Enhanced respiratory Pause (PenH), measured over 3-6 h. PenH can be conceptualized as the phase shift of the thoracic flow and the nasal flow curves indicating respiratory dysfunction pointing to airway resistance.…”

Section: Methodsmentioning

confidence: 99%

“…The lungs were fixed in 4% buffered formaldehyde for standard microscopic analysis, 3 mm sections were stained with haematoxylin and eosin (H&E) [62]. Neutrophil and erythrocyte accumulation in alveoli, disruption of alveolar septae and activation of alveolar epithelial cells were quantified using a semi-quantitative score with increasing severity of changes (0-5) as described previously [6,63]. Groups of 5-8 mice were included in each experiment and ten randomly selected high-power fields (400 Â magnifications) per animal were analyzed.…”

Section: Microscopy and Mpo Activity In Lungmentioning

confidence: 99%

“…2009. 39: 1587-1596 DOI 10.1002 Innate immunity 1587 function and bronchoconstriction, cytokine and chemokine production, PMN recruitment, increased permeability of the alveolar epithelium and the associated endothelium [3][4][5][6]. TLR4 [7], together with MD-2, LPS-binding protein and CD14 detect endotoxins and play a critical role in the initiation of the pulmonary response to systemic and mucosal endotoxin administration [5,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

et al. 2009

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Bacterial products (such as endotoxins and flagellin) trigger innate immune responses through TLRs. Flagellin-induced signalling involves TLR5 and MyD88 and, according to some reports, TLR4. Whereas epithelial and dendritic cells are stimulated by flagellin in vitro, the cell contribution to the in vivo response is still unclear. Here, we studied the respective roles of radioresistant and radiosensitive cells in flagellin-induced airway inflammation in mice. We found that i.n. delivery of flagellin elicits a transient change in respiratory function and an acute, pro-inflammatory response in the lungs, characterized by TLR5-and MyD88-dependent chemokine secretion and neutrophil recruitment. In contrast, TLR4, CD14 and TRIF were not essential for flagellin-mediated responses, indicating that TLR4 does not cooperate with TLR5 in the lungs. Respiratory function, chemokine secretion and airway infiltration by neutrophils were dependent on radioresistant, TLR5-expressing cells. Furthermore, lung haematopoietic cells also responded to flagellin by activating TNF-a production. We suggest that the radioresistant lung epithelial cells are essential for initiating early, TLR5-dependent signalling in response to flagellin and thus triggering the lung's innate immune responses.Key words: Chemokine . Epithelium . Flagellin . Lung inflammation . TLR5 IntroductionUpon challenge with respiratory pathogens, the airways rapidly develop a pro-inflammatory response initiated by environmental agents including microbe-associated molecular patterns such as Gram-negative bacteria LPS or endotoxins. This proinflammatory reaction plays an important role in the innate defense against respiratory pathogens [1,2]. Physiological changes induced by endotoxin inhalation include pulmonary Ã These authors contributed equally to this work. Eur. J. Immunol. 2009. 39: 1587-1596 DOI 10.1002 Innate immunity 1587 function and bronchoconstriction, cytokine and chemokine production, PMN recruitment, increased permeability of the alveolar epithelium and the associated endothelium [3][4][5][6]. TLR4 [7], together with MD-2, LPS-binding protein and CD14 detect endotoxins and play a critical role in the initiation of the pulmonary response to systemic and mucosal endotoxin administration [5,[8][9][10]. The pulmonary inflammation to endotoxin involves TLR4 signalling in both the parenchyma cells like endothelial and epithelial cells and the haematopoietic cells, i.e. monocytes, dendritic cells and neutrophils [11]. In addition, TLR4 signalling contributes to the development and progression of chronic respiratory disease including asthma [12][13][14][15][16].Flagellin is the major constituent of flagella from Gramnegative and Gram-positive bacteria. TLR5 has been identified as the main pattern recognition receptor required for flagellinmediated immune signalling [17]. TLR5 signalling depends on MyD88 and results in activation of MAPK, nuclear translocation of NF-kB and production of various pro-inflammatory cytokines and chemokines [18]. Moreover, a previous ...

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Barrier Enhancing Signals in Pulmonary Edema

Birukov

Zebda

Birukova

2013

Comprehensive Physiology

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Increased endothelial permeability and reduction of alveolar liquid clearance capacity are two leading pathogenic mechanisms of pulmonary edema, which is a major complication of acute lung injury, severe pneumonia, and acute respiratory distress syndrome, the pathologies characterized by unacceptably high rates of morbidity and mortality. Besides the success in protective ventilation strategies, no efficient pharmacological approaches exist to treat this devastating condition. Understanding of fundamental mechanisms involved in regulation of endothelial permeability is essential for development of barrier protective therapeutic strategies. Ongoing studies characterized specific barrier protective mechanisms and identified intracellular targets directly involved in regulation of endothelial permeability. Growing evidence suggests that, although each protective agonist triggers a unique pattern of signaling pathways, selected common mechanisms contributing to endothelial barrier protection may be shared by different barrier protective agents. Therefore, understanding of basic barrier protective mechanisms in pulmonary endothelium is essential for selection of optimal treatment of pulmonary edema of different etiology. This article focuses on mechanisms of lung vascular permeability, reviews major intracellular signaling cascades involved in endothelial monolayer barrier preservation and summarizes a current knowledge regarding recently identified compounds which either reduce pulmonary endothelial barrier disruption and hyperpermeability, or reverse preexisting lung vascular barrier compromise induced by pathologic insults.

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Dual Effects of p38 MAPK on TNF-Dependent Bronchoconstriction and TNF-Independent Neutrophil Recruitment in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

Cited by 93 publications

References 38 publications

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

Barrier Enhancing Signals in Pulmonary Edema

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