scholarly journals Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione

2008 ◽  
Vol 295 (4) ◽  
pp. L624-L636 ◽  
Author(s):  
Carolyn J. Baglole ◽  
Patricia J. Sime ◽  
Richard P. Phipps
Keyword(s):  
Cigarette Smoke ◽  
Heme Oxygenase ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Nuclear Accumulation ◽  
Heme Oxygenase 1 ◽  
Induced Expression ◽  
Human Lung Fibroblast ◽  
Human Lung Fibroblasts ◽  
Intracellular Glutathione

Fibroblasts are key structural cells that can be damaged by cigarette smoke. Cigarette smoke contains many components capable of eliciting oxidative stress, which may induce heme oxygenase (HO)-1, a cytoprotective enzyme. There are no data on HO-1 expression in primary human lung fibroblasts after cigarette smoke extract (CSE) exposure. We hypothesized that human lung fibroblasts exposed to cigarette smoke would increase HO-1 though changes in intracellular glutathione (GSH). Primary human lung fibroblasts were exposed to CSE, and changes in HO-1 expression and GSH levels were assessed. CSE induced a time- and dose-dependent increase in expression of HO-1, but not HO-2 or biliverdin reductase, in two different primary human lung fibroblast strains, a novel finding. This induction of HO-1 paralleled a decrease in intracellular GSH, and a sustained reduction in GSH resulted in a dramatic increase in HO-1. Treatment with the antioxidants N-acetyl-l-cysteine or GSH reduced the expression of HO-1 induced by CSE. We also examined the signal transduction mechanism responsible for HO-1 induction. Nuclear factor erythroid-derived 2, like 2 (Nrf2) was not involved in HO-1 induction by CSE. Activator protein-1 (AP-1) is a redox-sensitive transcription factor shown in other systems to regulate HO-1 expression. CSE exposure resulted in nuclear accumulation of c-Fos and c-Jun, two key AP-1 components. Reduction of c-Fos and c-Jun nuclear translocation by SP-600125 attenuated the CSE-induced expression of HO-1. These data support the concept that changes in the cellular redox status brought on by cigarette smoke induce HO-1 in fibroblasts. This increase in HO-1 may help protect against cigarette smoke-induced inflammation and/or cell death.

scholarly journals Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A) activity in human lung fibroblasts

2007 ◽  
Vol 8 (1) ◽  
Author(s):  
Giampiero La Rocca ◽  
Rita Anzalone ◽  
Francesca Magno ◽  
Felicia Farina ◽  
Francesco Cappello ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Human Lung ◽  
Smoke Exposure ◽  
Lung Fibroblasts ◽  
Cigarette Smoke Exposure ◽  
Gelatinase A ◽  
Human Lung Fibroblasts

scholarly journals Peroxisome proliferator-activated receptor-γ ligands induce heme oxygenase-1 in lung fibroblasts by a PPARγ-independent, glutathione-dependent mechanism

2009 ◽  
Vol 297 (5) ◽  
pp. L912-L919 ◽  
Author(s):  
Heather E. Ferguson ◽  
Thomas H. Thatcher ◽  
Keith C. Olsen ◽  
Tatiana M. Garcia-Bates ◽  
Carolyn J. Baglole ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Fibroblasts ◽  
Heme Oxygenase 1 ◽  
Peroxisome Proliferator ◽  
Covalent Bonds ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Lung Fibroblasts ◽  
Thiol Antioxidant ◽  
Dependent Mechanism

Oxidative stress plays an important role in the pathogenesis of pulmonary fibrosis. Heme oxygenase-1 (HO-1) is a key antioxidant enzyme, and overexpression of HO-1 significantly decreases lung inflammation and fibrosis in animal models. Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor that regulates adipogenesis, insulin sensitization, and inflammation. We report here that the PPARγ ligands 15d-PGJ2 and 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), which have potent antifibrotic effects in vitro, also strongly induce HO-1 expression in primary human lung fibroblasts. Pharmacological and genetic approaches are used to demonstrate that induction of HO-1 is PPARγ independent. Upregulation of HO-1 coincides with decreased intracellular glutathione (GSH) levels and can be inhibited by N-acetyl cysteine (NAC), a thiol antioxidant and GSH precursor. Upregulation of HO-1 is not inhibited by Trolox, a non-thiol antioxidant, and does not involve the transcription factors AP-1 or Nrf2. CDDO and 15d-PGJ2 contain an α/β unsaturated ketone that acts as an electrophilic center that can form covalent bonds with free reduced thiols. Rosiglitazone, a PPARγ ligand that lacks an electrophilic center, does not induce HO-1. These data suggest that in human lung fibroblasts, 15d-PGJ2 and CDDO induce HO-1 via a GSH-dependent mechanism involving the formation of covalent bonds between 15d-PGJ2 or CDDO and GSH. Inhibiting HO-1 upregulation with NAC has only a small effect on the antifibrotic properties of 15d-PGJ2 and CDDO in vitro. These results suggest that CDDO and similar electrophilic PPARγ ligands may have great clinical potential as antifibrotic agents, not only through direct effects on fibroblast differentiation and function, but indirectly by bolstering antioxidant defenses.

Tobacco smoke reduces viability in human lung fibroblasts: protective effect of glutathioneS-transferase P1

2001 ◽  
Vol 280 (6) ◽  
pp. L1189-L1195 ◽  
Author(s):  
Takeo Ishii ◽  
Takeshi Matsuse ◽  
Hiroko Igarashi ◽  
Michiaki Masuda ◽  
Shinji Teramoto ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Lung Diseases ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Protective Effects ◽  
Glutathione S Transferase ◽  
Cytotoxic Effects ◽  
Human Lung Fibroblast ◽  
Transient Overexpression ◽  
Induced Apoptosis

Cigarette smoking is thought to be a major risk factor in various lung diseases including lung cancer and emphysema. However, the direct effect of cigarette smoke on the viability of lung-derived cells has not been fully elucidated. In this study, we investigated the viability of human lung fibroblast-derived (HFL1) cells to different concentrations of cigarette smoke extract (CSE). CSE induced apoptosis at lower concentrations (10–25%) and necrosis at higher concentrations (50–100%). We also examined the effects of glutathione S-transferase P1 (GSTP1), one of the xenobiotic metabolizing and antioxidant enzymes in the lung, against the cytotoxicity of CSE. Our results indicated that the level of HFL1 cell death was decreased by transfection with a GSTP1 expression vector and was increased by GSTP1 antisense vector transfection. Therefore, transient overexpression and underexpression of GSTP1 appeared to inhibit and enhance the cytotoxic effects of CSE on HFL1 cells, suggesting that GSTP1 may have protective effects against cigarette smoke in the airway cells.

scholarly journals Ninjinyoeito Ameliorated Cigarette Smoke Extract-induced Apoptosis and Inflammation Through JNK Signaling Inhibition in Human Lung Fibroblasts

2021 ◽  
Author(s):  
Kenta Murata ◽  
Nina Fujita ◽  
Ryuji Takahashi
Keyword(s):  
Lung Injury ◽  
Cigarette Smoke ◽  
Human Lung ◽  
Cigarette Smoke Extract ◽  
Lung Fibroblasts ◽  
Ros Production ◽  
Jnk Signaling ◽  
Human Lung Fibroblasts ◽  
Induced Apoptosis ◽  
Apoptosis And Inflammation

Abstract BackgroundCigarette smoke is a major risk factor for various lung diseases, such as chronic obstructive pulmonary disease (COPD). Ninjinyoeito (NYT), a traditional Chinese medicine, has been prescribed for patients with post-illness or post-operative weakness, fatigue, loss of appetite, rash, cold limbs, and anemia. In addition to its traditional use, NYT has been prescribed for treating frailty in gastrointestinal, respiratory, and urinary functions. Further, NYT treatment can ameliorate cigarette smoke-induced lung injury, which is a destructive index in mice; however, the detailed underlying mechanism remains unknown. PurposeThe purpose of this study was to investigate whether NYT ameliorates cigarette smoke-induced lung injury and inflammation in human lung fibroblasts and determine its mechanism of action. MethodsWe prepared a cigarette smoke extract (CSE) from commercially available cigarettes to induce cell injury and inflammation in the human lung fibroblast cell line HFL1. The cells were pretreated with NYT for 24 h prior to CSE exposure. Cytotoxicity and cell viability were measured by lactate dehydrogenase (LDH) cytotoxicity assay and cell counting kit (CCK)-8. IL-8 level in the cell culture medium was measured by performing Enzyme-Linked Immuno Sorbent Assay (ELISA). To clarify the mechanisms of NYT, we used CellROX Green Reagent for reactive oxygen species (ROS) production and western blotting analysis for cell signaling.ResultsExposure of HFL1 cells to CSE for 24 h induced apoptosis and interleukin (IL)-8 release. Pretreatment with NYT inhibited apoptosis and IL-8 release. Furthermore, CSE exposure for 24 h increased the production of ROS and phosphorylation levels of p38 and JNK. Pretreatment with NYT only inhibited CSE-induced JNK phosphorylation, and not ROS production and p38 phosphorylation. These results suggest that NYT acts as a JNK-specific inhibitor.ConclusionNYT treatment ameliorated CSE-induced apoptosis and inflammation by inhibiting the JNK signaling pathway. Finally, these results suggest that NYT may be a promising therapeutic agent for patients with COPD.

Cigarette smoke extract induces ER stress in human lung fibroblasts from COPD patients and healthy subjects

2019 ◽  
Author(s):  
Martin Ryde ◽  
Rebecca Hillerström ◽  
Anni Malm ◽  
Gunilla Westergren-Thorsson ◽  
Leif Bjermer ◽  
...  
Keyword(s):  
Er Stress ◽  
Cigarette Smoke ◽  
Healthy Subjects ◽  
Human Lung ◽  
Cigarette Smoke Extract ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Copd Patients
Sign in / Sign up

Export Citation Format

Share Document