Advertisement

Topics

PARP inhibition by olaparib alleviates chronic asthma-associated remodeling features via modulating inflammasome signaling in mice.

08:00 EDT 9th April 2019 | BioPortfolio

Summary of "PARP inhibition by olaparib alleviates chronic asthma-associated remodeling features via modulating inflammasome signaling in mice."

Despite the reported role of poly(ADP-ribose) polymerase (PARP) in asthma inflammation, its contribution during remodeling is not clearly known. The main aim of the current investigation was to examine the potential of olaparib, a pharmacological inhibitor of PARP against airway remodeling using an ovalbumin (OVA)-based murine model of chronic asthma. The results demonstrated that post-challenge olaparib treatment (5 mg/kg i.p., 30 min after OVA exposure) for six weeks (3 days/week) attenuates inflammation, mucus production, and collagen deposition in lungs. Additionally, olaparib blunted the protein expression of STAT-6 and GATA-3 considerably along with a modest reduction in p65-NF-κB phosphorylation. Furthermore, olaparib normalized the OVA-induced redox imbalance as reflected by data on reactive oxygen species, malondialdehyde, protein carbonyls, and reduced glutathione/oxidized glutathione ratio. Interestingly, the protection offered by olaparib was further linked with the altered level of NLRP3 inflammasome-mediated IL-1β release and consequent expression of its downstream targets matrix metalloproteinase-9 and transforming growth factor beta. Suppressed collagen deposition in the lungs correlates well with the reduced expression of vimentin upon olaparib treatment. Finally, olaparib restored the expression of histone deacetylase 2, a steroid-responsive element in asthma. Overall, results suggest that olaparib prevents OVA-induced airway inflammation as well as remodeling via modulating inflammasome signaling in mice. © 2019 IUBMB Life, 1-11, 2019.

Affiliation

Journal Details

This article was published in the following journal.

Name: IUBMB life
ISSN: 1521-6551
Pages:

Links

DeepDyve research library

PubMed Articles [13032 Associated PubMed Articles listed on BioPortfolio]

PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.

PARP inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for ...

Design and synthesis of novel PARP-1 inhibitors based on pyridopyridazinone scaffold.

Various pyridopyridazinone derivatives were designed as Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. The pyridopyridazinone scaffold was used as an isostere of the phthalazine nucleus of the lea...

Bu-Shen-Yi-Qi formula ameliorates airway remodeling in murine chronic asthma by modulating airway inflammation and oxidative stress in the lung.

Bu-Shen-Yi-Qi formula (BSYQF) could suppress chronic airway inflammation according to previous studies. However, there is relatively little direct experimental evidence to evaluate the effects of BSYQ...

Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations.

Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, are being explored as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) in men harboring mutations in homol...

Real-World Use and Outcomes of Olaparib: a Population-Based Cohort Study.

Although olaparib, the first poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor approved, has been used in routine clinical practice for over three years, little has been published ...

Clinical Trials [9018 Associated Clinical Trials listed on BioPortfolio]

Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis

Olaparib has demonstrated preliminary efficacy in metastatic castration-resistant prostate cancer. In a trial of 49 evaluable patients treated with olaparib, 11 / 49 experienced a PSA resp...

ARQ761 + PARP Inhibitor in Refractory Solid Tumors

Open Label, dose escalation in a 3+3 study design to establish the RP2D of the combination of ARQ761 and a PARP inhibitor, Olaparib

Olaparib for PAH: a Multicenter Clinical Trial

The main OBJECTIVE of this proposal is to extend our preclinical findings on the role of DNA damage and poly(ADP-ribose) polymerases (PARP) inhibition as a therapy for a devastating diseas...

Role of Extracellular Matrix in the Development of Airway Remodeling in Asthma

Asthma is a major noncommunicable chronic inflammatory disorder which is characterized by airway inflammation and related to pathological modifications of the bronchial wall structure so c...

Targeting Resistant Prostate Cancer With ATR and PARP Inhibition (TRAP Trial)

The purpose of this study is to test the effectiveness (how well the drugs work), safety, and tolerability of the investigational drug combination of olaparib and AZD6738 for all patients ...

Medical and Biotech [MESH] Definitions

A lectin that binds CHITIN, but lacks chitinase activity. It may be involved in tissue remodeling and cellular responses to the environment, including the response of type 2 HELPER T-CELLS to INFLAMMATION and sensitization to ALLERGENS. Mutations in the CHI3L1 gene are associated with ASTHMA.

Diseases of long duration and generally slow progression. The four main types of noncommunicable diseases are CARDIOVASCULAR DISEASES (e.g., heart attacks and stroke), CANCER, chronic respiratory diseases (e.g., CHRONIC OBSTRUCTIVE PULMONARY DISEASE and ASTHMA) and DIABETES MELLITUS.

An ADRENERGIC BETA-2 RECEPTOR AGONIST with a prolonged duration of action. It is used to manage ASTHMA and in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE.

A selective ADRENERGIC BETA-2 RECEPTOR agonist that functions as a BRONCHODILATOR when administered by inhalation. It is used to manage the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE.

A enzyme complex involved in the remodeling of NUCLEOSOMES. The complex is comprised of at least seven subunits and includes both histone deacetylase and ATPase activities.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Allergies
The term allergy is used to describe a response, within the body, to a substance, which is not necessarily harmful in itself, but results in an immune response and a reaction that causes symptoms and disease in a predisposed person, which in turn can cau...

Polymerase Chain Reaction (PCR)
PCR (Polymerase Chain Reaction) uses the ability of DNA polymerase (enzymes that create DNA molecules by assembling nucleotides, the building blocks of DNA. These enzymes are essential to DNA replication and usually work in pairs to create two ident...


Searches Linking to this Article