Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction

Berndt, Annerose; Derksen, F. J.; Venta, Patrick J.; Ewart, Susan; Yuzbasiyan‐Gurkan, Vilma; Robinson, N. E.

doi:10.1152/ajplung.00394.2006

Cited by 56 publications

(44 citation statements)

References 48 publications

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“…Some of these chemokines include tumor necrosis factor α (TNF-α), IL-6, IL-8 and macrophage inflammatory protein-3α (MIP-3α), which are essential for phagocytes recruitment, granuloma formation, and clearance of bacterial infection in the lung (49,50). Although fundamental for pathogen clearance, over- or under-TLR signaling activation can be harmful to the host and leads to chronic inflammatory conditions such as asthma and COPD (26,51,52). …”

Section: Discussionmentioning

confidence: 99%

Airway Epithelial Expression of TLR5 Is Downregulated in Healthy Smokers and Smokers with Chronic Obstructive Pulmonary Disease

Wang

Ahmed

Wang

et al. 2012

The Journal of Immunology

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The toll-like receptors (TLRs) are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. Based on the knowledge that smokers are more susceptible to pulmonary infection and that the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th–12th order) epithelium from healthy nonsmokers (n=60), healthy smokers (n=73) and smokers with COPD (n=36). Using the criteria of detection call of present in ≥50%, 6 of 10 TLRs (1, 2, 3, 4, 5 and 8) were expressed. Compared to nonsmokers, the most striking change was for TLR5, which was down-regulated in healthy smokers (1.4-fold, p<10−10) and smokers with COPD (1.6-fold, p<10−11). TaqMan RT-PCR confirmed these observations. Bronchial biopsy immunofluorescence studies showed that TLR5 was expressed mainly on the apical side of the epithelium and was decreased in healthy smokers and smokers with COPD. In vitro, the level of TLR5 downstream genes, IL-6 and IL-8, were highly induced by flagellin in TLR5 high-expressing cells compared to TLR5 low-expressing cells. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced down-regulation of TLR5 may contribute to smoking-related susceptibility to airway infection, at least for flagellated bacteria.

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Section: Discussionmentioning

confidence: 99%

Airway Epithelial Expression of TLR5 Is Downregulated in Healthy Smokers and Smokers with Chronic Obstructive Pulmonary Disease

Wang

Ahmed

Wang

et al. 2012

The Journal of Immunology

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“…In a model of bacterial pneumonia that utilizes inhaled LPS, the uptake of LPS was observed in bronchial epithelial cells and was associated with increased TLR2 and TLR4 expression in the bronchial epithelium (97). Similarly, in an equine model of recurrent airway obstruction associated with inhaled endotoxin-rich stable dust, increased epithelial expression of TLR4 was observed and was associated with increased IL-8 expression by the airway epithelium (98). Taken together, these reports provide supportive evidence for an important role for epithelial TLR signaling in the pathogenesis of mucosal inflammation in the pulmonary system.…”

Section: Tlr-dependent Signaling In the Pulmonary Epithelium: A Role mentioning

confidence: 97%

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

Gribar

Richardson

Sodhi

et al. 2008

Mol Med

142

109

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Diseases of mucosal inflammation represent important causes of morbidity and mortality, and have led to intense research efforts to understand the factors that lead to their development. It is well accepted that a breakdown of the normally impermeant epithelial barrier of the intestine, the lung, and the kidney is associated with the development of inflammatory disease in these organs, yet significant controversy exists as to how this breakdown actually occurs, and how such a breakdown may lead to inflammation. In this regard, much work has focused upon the role of the epithelium as an "innocent bystander," a target of a leukocyte-mediated inflammatory cascade that leads to its destruction in the mucosal inflammatory process. However, recent evidence from a variety of laboratories indicates that the epithelium is not merely a passive component in the steps that lead to mucosal inflammation, but is a central participant in the process. In addressing this controversy, we and others have determined that epithelial cells express Toll-like receptors (TLRs) of the innate immune system, and that activation of TLRs by endogenous and exogenous ligands may play a central role in determining the balance between a state of "mucosal homeostasis," as is required for optimal organ function, and "mucosal injury," leading to mucosal inflammation and barrier breakdown. In particular, activation of TLRs within intestinal epithelial cells leads to the development of cellular injury and impairment in mucosal repair in the pathogenesis of intestinal inflammation, while activation of TLRs in the lung and kidney may participate in the development of pneumonitis and nephritis respectively. Recent work in support of these concepts is extensively reviewed, while essential areas of further study that are required to determine the significance of epithelial TLR signaling during states of health and disease are outlined.

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“…Thus, inhalation of the fungus alone may induce the production of proinflammatory, Th-1 and Th-2 cytokines, which may be sufficient to trigger the onset of respiratory airway inflammation (Rementeria et al 2005, Meier et al 2003, Berndt et al 2007. In our study, the progressive nature of the disease that was induced by fungus aspiration indicates that a specific immune response is needed and that this response is probably modulated by cytokines coming from the innate immune system.…”

Section: Discussionmentioning

confidence: 56%

Inhalation of Aspergillus fumigatus spores induces airway inflammation in mice in a similar manner as observed in Recurrent Airway Obstruction in horses

et al. 2011

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Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction

Abstract: Berndt A, Derksen FJ, Venta PJ, Ewart S, Yuzbasiyan-Gurkan V, Robinson NE. Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction.

Cited by 56 publications

References 48 publications

Airway Epithelial Expression of TLR5 Is Downregulated in Healthy Smokers and Smokers with Chronic Obstructive Pulmonary Disease

Airway Epithelial Expression of TLR5 Is Downregulated in Healthy Smokers and Smokers with Chronic Obstructive Pulmonary Disease

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

Inhalation of Aspergillus fumigatus spores induces airway inflammation in mice in a similar manner as observed in Recurrent Airway Obstruction in horses

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