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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.
This article was published in the following journal.
Name: IUBMB life
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 ...
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 (BSYQF) could suppress chronic airway inflammation according to previous studies. However, there is relatively little direct experimental evidence to evaluate the effects of BSYQ...
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...
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 ...
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...
Open Label, dose escalation in a 3+3 study design to establish the RP2D of the combination of ARQ761 and a PARP inhibitor, Olaparib
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...
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...
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 ...
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.
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...