Cigarette smoke increases Toll‐like receptor 4 and modifies lipopolysaccharide‐mediated responses in airway epithelial cells

Pace, Elisabetta; Ferraro, Maria; Siena, Liboria; Melis, Marcello; Montalbano, Angela Marina; Johnson, Malcolm; Bonsignore, Maria R.; Bonsignore, G; Gjomarkaj, Mark

doi:10.1111/j.1365-2567.2007.02788.x

Cited by 182 publications

(163 citation statements)

References 30 publications

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“…Exposure to cigarette smoke has been shown to increase TLR4 expression, leading to heightened CXCL8 production and additional recruitment of polymorphonuclear cells to the airways (69). In patients with CF, there is typically a hyperinflammatory state in the lungs, which is also seen in CF cell lines with increased CXCL8 and NF-kB signaling (28,70).…”

Section: Modification Of Tlr Signaling In Disease Statesmentioning

confidence: 89%

Innate Immunity in the Respiratory Epithelium

Parker

Prince

2011

Am J Respir Cell Mol Biol

393

404

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The airway epithelium represents the first point of contact for inhaled foreign organisms. The protective arsenal of the airway epithelium is provided in the form of physical barriers and a vast array of receptors and antimicrobial compounds that constitute the innate immune system. Many of the known innate immune receptors, including the Toll-like receptors and nucleotide oligomerization domain-like receptors, are expressed by the airway epithelium, which leads to the production of proinflammatory cytokines and chemokines that affect microorganisms directly and recruit immune cells, such as neutrophils and T cells, to the site of infection. The airway epithelium also produces a number of resident antimicrobial proteins, such as lysozyme, lactoferrin, and mucins, as well as a swathe of cationic proteins. Dysregulation of the airway epithelial innate immune system is associated with a number of medical conditions that can result in compromised immunity and chronic inflammation of the lung. This review focuses on the innate immune capabilities of the airway epithelium and its role in protecting the lung from infection as well as the outcomes when its function is compromised.

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Section: Modification Of Tlr Signaling In Disease Statesmentioning

confidence: 89%

Innate Immunity in the Respiratory Epithelium

Parker

Prince

2011

Am J Respir Cell Mol Biol

393

404

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“…Low-level NF-kB induction in isolated cells by cigarette smoke was often demonstrated with subconfluent cell testing, low smoke preparation concentrations, or shorter durations of exposure (28,33,39,40). In contrast, the impairment of NF-kB activation or function was often associated with confluent cells or treatment with higher levels of exposure to cigarette smoke, alone or in combination with other stimuli (28,(41)(42)(43). However, other reports showed that cigarette smoke alone exerts little effect on NF-kB activation or function (44,45).…”

Section: Discussionmentioning

confidence: 99%

Inhibition by Cigarette Smoke of Nuclear Factor-κB–Dependent Response to Bacteria in the Airway

Manzel¹,

Shi²,

O’Shaughnessy³

et al. 2011

Am J Respir Cell Mol Biol

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Although individuals exposed to cigarette smoke are more susceptible to respiratory infection, the effects of cigarette smoke on pulmonary defense are incompletely understood. Based on the observation that interactions between bacteria and host cells result in the expression of critical defense genes regulated by NF-kB, we hypothesized that cigarette smoke alters NF-kB function. In this study, primary human tracheobronchial epithelial cells were treated with cigarette smoke extract (CSE) and exposed to Haemophilus influenzae, and the effects of CSE on bacteria-induced signaling and gene expression were assessed. CSE inhibited high concentrations of induced NF-kB activation and the consequent expression of defense genes that occurred in airway epithelial cells in response to H. influenzae. This decreased activation of NF-kB was not attributable to cell loss or cytotoxicity. Glutathione augmentation of epithelial cells decreased the effects of CSE on NF-kB-dependent responses, as well as the effects on the inhibitor of kB and the inhibitor of kB kinase, which are upstream NF-kB regulators, suggesting the involvement of reactive oxygen species. The relevance of these findings for lung infection was confirmed using a mouse model of H. influenzae airway infection, in which decreased NF-kB pathway activation, keratinocyte chemoattractant (KC) chemokine expression, and neutrophil recruitment occurred in animals exposed to cigarette smoke. The results indicate that although cigarette smoke can cause inflammation in the lung, exposure to smoke inhibits the robust pulmonary defense response to H. influenzae, thereby providing one explanation for the increased susceptibility to respiratory bacterial infection in individuals exposed to cigarette smoke.

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“…Cell cultures were maintained in a humidified atmosphere of 5 % CO 2 in air at 37°C. Cell lines were cultured as previously reported in the presence of CSE (5 and 10 %; Pace et al 2008a) and in the presence and absence of FP (10 −4 , 10 −7 , 10 −8 and 10 −9 M; Sigma-Aldrich, St. Louis, MO) and CARB (10 −3 , 10 −4 , 10 −5 and 10 −8 M; Dompè, Italy; Garavaglia et al 2008). Three time points were initially tested: 2, 4 and 18 h. CARB was added 1 h before CSE cell stimulation.…”

Section: Stimulation Of Epithelial Cell Linesmentioning

confidence: 99%

“…In this regard, it has been demonstrated that upon cigarette smoke extracts (CSE) stimulation, the airway epithelium is able to release increased concentrations of IL-8, but reduced IFN-gamma-inducible protein 10 (Pace et al 2008a), thus amplifying the inflammatory and immune responses.…”

Section: Introductionmentioning

confidence: 99%

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

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Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10 −4 M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclearrelated factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10 −8 M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin Vpositive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSEmediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance.

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Cigarette smoke increases Toll‐like receptor 4 and modifies lipopolysaccharide‐mediated responses in airway epithelial cells

Cited by 182 publications

References 30 publications

Innate Immunity in the Respiratory Epithelium

Innate Immunity in the Respiratory Epithelium

Inhibition by Cigarette Smoke of Nuclear Factor-κB–Dependent Response to Bacteria in the Airway

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

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