Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema

Voss, Meike; Wolf, Lisa; Kamyschnikow, Andreas; Wonnenberg, Bodo; Honecker, Anja; Herr, Christian; Lepper, Philipp M.; Wegmann, Michael; Menger, Michael D.; Bals, Robert; Beißwenger, Christoph

doi:10.1152/ajplung.00388.2014

Cited by 23 publications

(29 citation statements)

References 47 publications

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“…Chronic CS exposure of mice leads to lung function decrease and structural lung damage [27, 60, 61]. In our chronic CS model, emphysema-like changes were not further increased in RAGE -/- mice.…”

Section: Discussionmentioning

confidence: 89%

“…To analyze a CS induced lung damage, eight week old female WT and RAGE -/- mice were exposed to the smoke of 3R4F cigarettes (College of Agriculture, Reference Cigarette Program, University of Kentucky, Lexington, Kentucky, USA) in a TE-10 smoking machine (Teague Enterprises, Woodland, California, USA) [27]. Mice were subjected to CS for 261 minutes /day, five days/week for six months.…”

Section: Methodsmentioning

confidence: 99%

“…For the evaluation of respiratory system mechanics, mice were analyzed using the FlexiVent system (Scireq, Montreal, Canada) for forced oscillation measurements as described earlier [27, 28]. Mice were anesthetized with ketamine (7 mg/kg, i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…The mean chord length was calculated using the Visiopharm Integrator System (Visiopharm, Hoersholm, Denmark) on an Olympus BX51 microscope equipped with an 8-position slide holder. Hematoxilin and eosin staining was done following standard protocols [27]. …”

Section: Methodsmentioning

confidence: 99%

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Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke

et al. 2017

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The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

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Section: Discussionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke

et al. 2017

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“…P. aeruginosa CFU values were determined by spreading appropriate dilutions of lung homogenates on agar plates (37). Lungs not subjected to BAL were fixed by instillation of PBS-buffered 4% formalin under a constant hydrostatic pressure of 30 cm for 15 min and placed in PBS-buffered 4% formalin for 24 h. The fixed lungs were embedded in 1% agarose and cut into regular slices of exactly the same thickness and embedded in paraffin (32). Hematoxylin/eosin staining was done using standard protocols.…”

Section: Methodsmentioning

confidence: 99%

IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acutePseudomonas aeruginosapneumonia

Wolf

Sapich

Honecker

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lung epithelial cells are suggested to promote pathogen-induced pulmonary inflammation by the release of chemokines, resulting in enhanced recruitment of circulating leukocytes. Recent studies have shown that the interleukin-17C (IL-17C) regulates innate immune functions of epithelial cells in an autocrine manner. The aim of this study was to investigate the contribution of IL-17C to pulmonary inflammation in a mouse model of acute Pseudomonas aeruginosa pneumonia. Infection with P. aeruginosa resulted in an increased expression of IL-17C in lung tissue of wild-type mice. Numbers of neutrophils and the expression of the neutrophil-recruiting chemokines keratinocyte-derived chemokine and macrophage inflammatory protein 2 were significantly decreased in lungs of IL-17C-deficient (IL-17C) mice infected with P. aeruginosa at 24 h. Systemic concentrations of interleukin-6 (IL-6) were significantly decreased in infected IL-17C mice at 24 h and the survival of IL-17C mice was significantly increased at 48 h. The expression of IL-17C was reduced in infected mice deficient for interleukin-17A (IL-17A), whereas pulmonary concentrations of IL-17A were not affected by the deficiency for IL-17C. Stimulation of primary alveolar epithelial cells with IL-17A resulted in a significantly increased expression of IL-17C in vitro. Our data suggest that IL-17A-mediated expression of epithelial IL-17C amplifies the release of chemokines by epithelial cells and thereby contributes to the recruitment of neutrophils and systemic inflammation during acute P. aeruginosa pneumonia.

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Intracellular and Extracellular Cytokines in A549 Cells and THP1 Cells Exposed to Cigarette Smoke

Hołownia

Wielgat

Rysiak

et al. 2016

Respiratory Medicine and Science

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Cigarette smoke (CS) activates inflammatory cells and increases cytokine levels producing local and systemic inflammation. To assess changes in intracellular and extracellular cytokine levels we used human epithelial (A549 cells) and monocyte (THP-1) cell lines grown for 24 h in cigarette smoke-conditioned media. Cytokines were assessed using immunostaining/flow cytometry and ELISA assay. In THP1cells, grown in CS-conditioned media, the intracellular interleukins IL-1β, IL-6, and IL-10 increased by more than tenfold, while less significant increases were found in A549 cells. IL-1α and IL-1β, but not IL-6 or IL-10, were increased in the culture media, while IL-2 was raised by about fivefold only in the culture medium of A549 cells. IL-4, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor alpha were undetectable, while only a slight increase was observed in extracellular IL-17A (by about 60 %) in the medium of A549 cells and by about 115 % in the medium of THP1 cells. The interferon gamma (IFNγ) was increased by about eightfold, but only in the medium of THP1 cells grown with CS. We conclude that IL-1 and INFγ are the key cytokines responsible for pro-inflammatory signaling in epithelial cells and monocytes, respectively, exposed to cigarette smoke.

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Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema

Cited by 23 publications

References 47 publications

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke

IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acutePseudomonas aeruginosapneumonia

Intracellular and Extracellular Cytokines in A549 Cells and THP1 Cells Exposed to Cigarette Smoke

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