Genetic deletion of IL-17A reduces cigarette smoke-induced inflammation and alveolar type II cell apoptosis

2014 ◽  
Vol 306 (2) ◽  
pp. L132-L143 ◽  
Author(s):  
Ying Chang ◽  
Laila Al-Alwan ◽  
Severine Audusseau ◽  
Fazila Chouiali ◽  
Juna Carlevaro-Fita ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cigarette Smoke ◽  
Cell Apoptosis ◽  
Alveolar Type ◽  
Inflammatory Disorder ◽  
Type Ii ◽  
Wild Type ◽  
Alveolar Cells ◽  
Alveolar Cell ◽  
Type Ii Alveolar Cells

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked by relative resistance to steroids. Inflammation and apoptosis have been suggested to be important mechanisms for COPD. Interleukin (IL)-17 superfamily has been associated with chronic inflammation and diminished responses to steroids. It is reasonable to consider that IL-17 may play a role in the pathogenesis of COPD. In this study, we examined IL-17 expression in mice exposed to cigarette smoke (CS) and investigated the contribution of IL-17 to CS-induced inflammation and alveolar cell apoptosis in IL-17−/− mice. After exposing wild-type and IL-17−/− mice to mainstream CS for 4 wk, IL-17A, but not IL-17F, expression was increased in mice upon CS exposure. Neutrophil infiltration in the lungs of IL-17−/− mice was significantly decreased. In IL-17−/− mice, there is reduced expression of IL-6, macrophage inflammatory protein-2, and matrix metalloproteinase-12 compared with wild-type mice after CS exposure. The number of apoptotic type II alveolar cells was significantly increased in CS-exposed wild-type mice but not in IL-17−/− mice. The effect of IL-17A on type II alveolar cell apoptosis was confirmed in vitro through either addition of IL-17A or transient knockdown of IL-17A by small-interfering RNA transfection in type II alveolar cells. These findings suggest that IL-17A plays an important role in the inflammatory response to CS exposure through increased multiple inflammatory mediators. Moreover, IL-17 may also contribute to type II alveolar cell apoptosis. This study opens a new option in targeting IL-17A to modulate inflammatory response to CS and may be the bases for new therapy for COPD.

PM2.5-induced lung inflammation in mice: Differences of inflammatory response in macrophages and type II alveolar cells

2017 ◽  
Vol 37 (10) ◽  
pp. 1203-1218 ◽  
Author(s):  
Miao He ◽  
Takamichi Ichinose ◽  
Seiichi Yoshida ◽  
Tomohiro Ito ◽  
Cuiying He ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lung Inflammation ◽  
Type Ii ◽  
Alveolar Cells ◽  
Type Ii Alveolar Cells

Integrin mediation of type II cell adherence to provisional matrix proteins

1996 ◽  
Vol 271 (2) ◽  
pp. L277-L286 ◽  
Author(s):  
H. J. Kim ◽  
D. H. Ingbar ◽  
C. A. Henke
Keyword(s):  
Cell Adhesion ◽  
Matrix Proteins ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Cells ◽  
Type Ii Cell ◽  
Type Ii Alveolar Cells ◽  
Alpha V Beta 3

Lung injury causes alveolar type I epithelial cell death, basement membrane denudation, and alveolar flooding with serum fibronectin and fibrinogen. For successful restoration of normal architecture, the epithelium must be regenerated from progenitor type II alveolar cells. Using adhesion assays, we examined whether type II alveolar cells adhere to the provisional matrix proteins fibronectin, fibrinogen, and fibrin, and whether integrins mediate this adherence. Rat type II cells adhered to fibronectin, vitronectin, fibrinogen, and fibrin. Synthetic RGD (arginine-glycine-aspartic acid) peptide blocked this adhesion. Flow cytometry and Western analysis indicated that type II cells expressed beta 1- and alpha v beta 3-integrins. Anti-beta 1-and anti-alpha v beta 3-integrin antibodies blocked type II cell adhesion to fibronectin and to fibronectin and fibrinogen, respectively. In summary, type II cells adhered to fibronectin, fibrinogen, and fibrin, and adhesion was partially mediated by integrins. This study provides the first evidence of type II cell adhesion to fibrin gels and vitronectin, beta 1- and alpha v beta 3-integrin mediation of type II cell adhesion, and the presence of the alpha v beta 3-integrin on type II epithelial cells.

scholarly journals The relationship between DJ-1 and S100A8 in human primary alveolar type II cells in emphysema

2019 ◽  
Vol 317 (6) ◽  
pp. L791-L804
Author(s):  
Chih-Ru Lin ◽  
Karim Bahmed ◽  
Dhanendra Tomar ◽  
Nathaniel Marchetti ◽  
Gerard J. Criner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Cigarette Smoke Extract ◽  
Airflow Limitation ◽  
Alveolar Type ◽  
Alveolar Wall ◽  
Type Ii ◽  
Atii Cell

Pulmonary emphysema is characterized by alveolar type II (ATII) cell death, destruction of alveolar wall septa, and irreversible airflow limitation. Cigarette smoke induces oxidative stress and is the main risk factor for this disease development. ATII cells isolated from nonsmokers, smokers, and patients with emphysema were used for this study. ATII cell apoptosis in individuals with this disease was detected. DJ-1 and S100A8 have cytoprotective functions against oxidative stress-induced cell injury. Reduced DJ-1 and S100A8 interaction was found in ATII cells in patients with emphysema. The molecular function of S100A8 was determined by an analysis of the oxidation status of its cysteine residues using chemoselective probes. Decreased S100A8 sulfination was observed in emphysema patients. In addition, its lower levels correlated with higher cell apoptosis induced by cigarette smoke extract in vitro. Cysteine at position 106 within DJ-1 is a central redox-sensitive residue. DJ-1 C106A mutant construct abolished the cytoprotective activity of DJ-1 against cell injury induced by cigarette smoke extract. Furthermore, a molecular and complementary relationship between DJ-1 and S100A8 was detected using gain- and loss-of-function studies. DJ-1 knockdown sensitized cells to apoptosis induced by cigarette smoke extract, and S100A8 overexpression provided cytoprotection in the absence of DJ-1. DJ-1 knockout mice were more susceptible to ATII cell apoptosis induced by cigarette smoke compared with wild-type mice. Our results indicate that the impairment of DJ-1 and S100A8 function may contribute to cigarette smoke-induced ATII cell injury and emphysema pathogenesis.

scholarly journals An improved method for the isolation of rat alveolar type II lung cells: Use in the Comet assay to determine DNA damage induced by cigarette smoke

2015 ◽  
Vol 72 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Annette Dalrymple ◽  
Patricia Ordoñez ◽  
David Thorne ◽  
Debbie Dillon ◽  
Clive Meredith
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Cigarette Smoke ◽  
Lung Cells ◽  
Alveolar Type ◽  
Type Ii ◽  
Improved Method

scholarly journals Bradykinin Stimulates Type II Alveolar Cells to Release Neutrophil and Monocyte Chemotactic Activity and Inflammatory Cytokines

1998 ◽  
Vol 153 (6) ◽  
pp. 1885-1893 ◽  
Author(s):  
Sekiya Koyama ◽  
Etsuro Sato ◽  
Hiroshi Nomura ◽  
Keishi Kubo ◽  
Masakazu Miura ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Chemotactic Activity ◽  
Type Ii ◽  
Alveolar Cells ◽  
Type Ii Alveolar Cells

scholarly journals CD8+ T Cell–mediated Injury In Vivo Progresses in the Absence of Effector T Cells

2001 ◽  
Vol 194 (12) ◽  
pp. 1835-1846 ◽  
Author(s):  
Barbara A. Small ◽  
Sarah A. Dressel ◽  
Christopher W. Lawrence ◽  
Donald R. Drake ◽  
Mark H. Stoler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tissue Injury ◽  
Cd8 T Cell ◽  
Effector T Cells ◽  
Type Ii ◽  
Pulmonary Injury ◽  
Alveolar Cells ◽  
Type Ii Alveolar Cells

Tissue injury is a common sequela of acute virus infection localized to a specific organ such as the lung. Tissue injury is an immediate consequence of infection with lytic viruses. It can also result from the direct destruction of infected cells by effector CD8+ T lymphocytes and indirectly through the action of the T cell–derived proinflammatory cytokines and recruited inflammatory cells on infected and uninfected tissue. We have examined CD8+ T cell–mediated pulmonary injury in a transgenic model in which adoptively transferred, virus-specific cytotoxic T lymphocytes (CTLs) produce lethal, progressive pulmonary injury in recipient mice expressing the viral target transgene exclusively in the lungs. We have found that over the 4–5 day course of the development of lethal pulmonary injury, the effector CTLs, while necessary for the induction of injury, are present only transiently (24–48 h) in the lung. We provide evidence that the target of the antiviral CD8+ T cells, the transgene expressing type II alveolar cells, are not immediately destroyed by the effector T cells. Rather, after T cell–target interaction, the type II alveolar cells are stimulated to produce the chemokine monocyte chemoattractant protein 1. These results reinforce the concept that, in vivo, the cellular targets of specific CTLs may participate directly in the development of progressive tissue injury by activating in response to interaction with the T cells and producing proinflammatory mediators without sustained in vivo activation of CD8+ T cell effectors.

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