ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Protein phosphatase 2A regulates innate immune and proteolytic responses to cigarette smoke exposure in the lung.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Network-based analysis reveals novel gene signatures in peripheral blood of patients with chronic obstructive pulmonary disease.Respiratory research · 2017Trial
- Beyond Antioxidants: How Redox Pathways Shape Cellular Signaling and Disease Outcomes.Antioxidants (Basel, Switzerland) · 2025Review
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Cigarette smoke alters calcium flux to induce PP2A membrane trafficking and endothelial cell permeability.Scientific reports · 2024Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Small-Molecule Activation of Protein Phosphatase 2A Counters Bleomycin-Induced Fibrosis in Mice.ACS pharmacology & translational science · 2023Article
- Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Emphysema.American journal of respiratory cell and molecular biology · 2023Article
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Review
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- Article
- Network-based pharmacology to predict the mechanism ofInternational journal of clinical and experimental pathology · 2021Article
- Metformin Increases Protein Phosphatase 2A Activity in Primary Human Skeletal Muscle Cells Derived from Lean Healthy Participants.Journal of diabetes research · 2021Article
- Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics.Respiratory research · 2020Review
- PP2Ac Modulates AMPK-Mediated Induction of Autophagy inInternational journal of molecular sciences · 2019Article
- Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer.Respiratory research · 2019Review
- Phosphorylation-dependent modulation of CFTR macromolecular signalling complex activity by cigarette smoke condensate in airway epithelia.Scientific reports · 2019Article
- Protein Phosphatase 2A Reduces Cigarette Smoke-induced Cathepsin S and Loss of Lung Function.American journal of respiratory and critical care medicine · 2019Article
- Loss of myeloid-specific protein phosphatase 2A enhances lung injury and fibrosis and results in IL-10-dependent sensitization of epithelial cell apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- PP2ACα of Alveolar Macrophages Is a Novel Protective Factor for LPS-Induced Acute Respiratory Distress Syndrome.Inflammation · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Protein phosphatase 2A (PP2A) is the primary serine-threonine phosphatase of eukaryotic cells, and changes in its activity have been linked to neoplastic and neurodegenerative diseases. However, the role of PP2A in noncancerous lung diseases such as chronic obstructive pulmonary disease (COPD) has not been previously examined. This study determined that PP2A activity was significantly increased in the lungs of advanced emphysema subjects compared with age-matched controls. Furthermore, we found that cigarette smoke exposure increases PP2A activity in mouse lung in vivo and in primary human small airway epithelial (SAE) cells in vitro. In mice, intratracheal transfection of PP2A protein prior to cigarette smoke exposure prevented acute smoke-induced lung inflammation. Conversely, inhibiting PP2A activity during smoke exposure exacerbated inflammatory responses in the lung. To further determine how PP2A modulates the responses to cigarette smoke in the lung, enzyme levels were manipulated in SAE cells using protein transfection and short hairpin RNA (shRNA) techniques. Increasing PP2A activity in SAE cells via PP2A protein transfection downregulated cytokine expression and prevented the induction of proteases following cigarette smoke extract (CSE) treatment. Conversely, decreasing enzymatic activity by stably transfecting SAE cells with shRNA for the A subunit of PP2A exacerbated these smoke-mediated responses. This study establishes that PP2A induction by cigarette smoke modulates immune and proteolytic responses to cigarette smoke exposure. Together, these findings suggest that manipulation of PP2A activity may be a plausible means to treat COPD and other inflammatory diseases.
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