Cutting Edge: Enhanced Pulmonary Clearance of <i>Pseudomonas aeruginosa</i> by Muc1 Knockout Mice

Lu, Wenju; Hisatsune, Akinori; Koga, Takeshi; Kato, Kosuke; Kuwahara, Ippei; Lillehoj, Erik P.; Chen, Wilbur; Cross, Alan S.; Gendler, Sandra J.; Gewirtz, Andrew T.; Kim, K. Chul

doi:10.4049/jimmunol.176.7.3890

Cited by 126 publications

(160 citation statements)

References 30 publications

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“…A similar biphasic response was previously reported when evaluating TNF-a production induced by the same flagellin concentrations in mouse alveolar macrophages. 34 As flagellin monomers can polymerize in solution under certain conditions, reconstituting flagellar fibers undistinguishable from native flagella, 35 it is possible that increasing FliC concentrations tend to more easily re-aggregate, reducing the ability of FliC preparation to prevent neutrophil apoptosis. On the other hand, it has been previously shown that flagellin induces self-tolerance by blocking the release of IRAK from the TLR5 complex in flagellin-tolerant cells.…”

Section: Discussionmentioning

confidence: 99%

Flagellin delays spontaneous human neutrophil apoptosis

Salamone

Petracca

Bass

et al. 2010

Laboratory Investigation

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Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella thyphimurim at concentrations found in pathological situations underwent a marked prevention of apoptosis. In contrast, Helicobacter pylori flagellin did not affect neutrophil survival, suggesting that Salmonella flagellin exerts the antiapoptotic effect by interacting with TLR5. The delaying in apoptosis mediated by Salmonella flagellin was coupled to higher expression levels of the antiapoptotic protein Mcl-1 and lower levels of activated caspase-3. Analysis of the signaling pathways indicated that Salmonella flagellin induced the activation of the p38 and ERK1/2 MAPK pathways as well as the PI3K/Akt pathway. Furthermore, it also stimulated IkBa degradation and the phosphorylation of the p65 subunit, suggesting that Salmonella flagellin also triggers NF-kB activation. Moreover, the pharmacological inhibition of ERK1/2 pathway and NF-kB activation partially prevented the antiapoptotic effects exerted by flagellin. Finally, the apoptotic delaying effect exerted by flagellin was also evidenced when neutrophils were cultured with whole heat-killed S. thyphimurim. Both a wild-type and an aflagellate mutant S. thyphimurim strain promoted neutrophil survival; however, when cultured in low bacteria/neutrophil ratios, the flagellate bacteria showed a higher capacity to inhibit neutrophil apoptosis, although both strains showed a similar ability to induce neutrophil activation. Taken together, our results indicate that flagellin delays neutrophil apoptosis by a mechanism partially dependent on the activation of ERK1/2 MAPK and NF-kB. The ability of flagellin to delay neutrophil apoptosis could contribute to perpetuate the inflammation during infections with flagellated bacteria.

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Section: Discussionmentioning

confidence: 99%

Flagellin delays spontaneous human neutrophil apoptosis

Salamone

Petracca

Bass

et al. 2010

Laboratory Investigation

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“…The PA infection and assessment of lung bacterial clearance were performed as we described previously [35]. Briefly, PA strain PA01…”

Section: Pa Infectionmentioning

confidence: 99%

Bone morphogenetic protein 4 inhibits liposaccharide‐induced inflammation in the airway

Wang

et al. 2014

Eur J Immunol

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Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-β superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-α. BMP4 mutant (BMP4 Keywords: Airway inflammation r BMP4 r LPS r Lung function r Pseudomonas aeruginosaAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionInflammation is a complex response that can be both defensive and harmful to the body. Although the primary role of inflammaCorrespondence: Prof. Wenju Lu e-mail: wlu92@yahoo.com tion is to eliminate the detrimental factors in tissues, the out-ofcontrolled inflammatory responses will lead to tissue damage that is even more harmful than the primary disease condition. Establishment of inflammatory cascades includes the release of both * These authors contributed equally to this work.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 3284 Zhengtu Li et al. Eur. J. Immunol. 2014. 44: 3283-3294 pro-and anti-inflammatory mediators and the maturation, activation, and migration of the responding inflammatory cells [1]. The excessive inflammation in the lung causes lung injury that includes reduced alveolar-capillary barrier function, increased pulmonary vascular permeability, leukocyte infiltration into the alveolar space, etc. [2]. If the inflammatory factors cannot be cleared out timely, it makes the acute inflammation turn into chronic condition [3]. Accumulating evidence indicates that transforming growth factor β (TGF-β) plays a determining role in regulating both innate and acquired immunity [4]. TGF-β1 null mice exhibit widespread lethal inflammation in tissue, primarily in the heart and lung [5]. In addition, TGF-β1 stimulates fibroblast proliferation, promoting airway remodeling during chronic lung inflammation associated with asthma and chronic obstructive pulmonary disease (COPD) [6]. Bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to TGF-β superfamily members [7]. Owing to their chemotactic activity on fibroblasts, myocytes, and inflammatory cells, BMPs were also considered to influence inflammatory processes in adults [8]. Bone morphogenetic protein 4 (BMP4), a member of the BMPs family, is primarily expressed in airway epithelial cells and plays a key role in the early stage of lung development [9]. BMP4 was demonstrated being upregulated in ovabumin-induced inflammation in mouse lung [8]. However, the role of BMP4 in lung inflammation, particularly in lung innate immunity is unknown.In this study, we hypothesized that BMP4 might participate in regulating the innate immune responses to bacterial infection. We examined the lung BMP4 expression during LPS-induced inflammation. Moreover, we compared the LPS-induced and Pseudomonas aeruginosa (PA) induced airway inflammation and pulmonary bacterial...

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“…Stimulated AMs, secreting a number of pro-inflammatory cytokines and chemokines, play a direct role in the recruitment of neutrophils [26,34].…”

Section: Airway Inflammation and Infectionmentioning

confidence: 99%

Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms

Fuschillo¹,

Felice²,

Balzano³

2008

Eur Respir J

184

124

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Bronchiectasis is a chronic and debilitating lung disease, characterised by irreversible dilatation of the bronchi as consequence of airway injury and remodelling due to recurrent or chronic airway inflammation and infection. The underlying aetiologies include autoimmune diseases, severe infections, genetic abnormalities and acquired disorders.The pathogenesis of bronchiectasis is poorly understood. Three distinct pathogenetic elements, namely infection, inflammation and enzymatic actions, which interact with each other, have been implicated in the pathophysiology of bronchiectasis.Some recent observations indicate that airway inflammation in bronchiectasis comes from a deregulated cytokine network independent of bacterial airway colonisation.In the present review, current knowledge about cellular and molecular inflammatory events in the dynamic process of host-pathogen interaction that are thought to play a relevant role in the pathogenic mechanisms of airway wall destruction leading to bronchiectasis are discussed.

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Cutting Edge: Enhanced Pulmonary Clearance of Pseudomonas aeruginosa by Muc1 Knockout Mice

Cited by 126 publications

References 30 publications

Flagellin delays spontaneous human neutrophil apoptosis

Flagellin delays spontaneous human neutrophil apoptosis

Bone morphogenetic protein 4 inhibits liposaccharide‐induced inflammation in the airway

Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms

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