Poly(ADP-Ribose)Polymerase-1 in Lung Inflammatory Disorders: A Review

Abstract

Asthma, acute lung injury (ALI), and chronic obstructive pulmonary disease (COPD) are lung inflammatory disorders with a common outcome, that is, difficulty in breathing. Corticosteroids, a class of potent anti-inflammatory drugs, have shown less success in the treatment/management of these disorders, particularly ALI and COPD; thus, alternative therapies are needed. Poly(ADP-ribose)polymerases (PARPs) are the post-translational modifying enzymes with a primary role in DNA repair. During the last two decades, several studies have reported the critical role played by PARPs in a good of inflammatory disorders. In the current review, the studies that address the role of PARPs in asthma, ALI, and COPD have been discussed. Among the different members of the family, PARP-1 emerges as a key player in the orchestration of lung inflammation in asthma and ALI. In addition, PARP activation seems to be associated with the progression of COPD. Furthermore, PARP-14 seems to play a crucial role in asthma. STAT-6 and GATA-3 are reported to be central players in PARP-1-mediated eosinophilic inflammation in asthma. Interestingly, oxidative stress–PARP-1–NF-κB axis appears to be tightly linked with inflammatory response in all three-lung diseases despite their distinct pathophysiologies. The present review sheds light on PARP-1-regulated factors, which may be common or differential players in asthma/ALI/COPD and put forward our prospective for future studies.

Treatment with 3-aminobenzamide during ex vivo lung perfusion of damaged rat lungs reduces graft injury and dysfunction after transplantation

“…It must be stressed that the degree of cytokine accumulation during EVLP correlates with poor outcomes after LTx . Our finding of reduced cytokines with 3‐AB implicates therefore a key role of PARP in this process, in line with the reported pro‐inflammatory actions of PARP, notably in the lungs …”

“…22 Our finding of reduced cytokines with 3-AB implicates therefore a key role of PARP in this process, in line with the reported pro-inflammatory actions of PARP, notably in the lungs. 23,24 To be clinically relevant, the effects of any drug on a lung graft ex vivo should translate into an improved outcome after LTx in vivo. To date, such evidence is scarce.…”

A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

“…In addition, the FDA-approved PARP1 inhibitor, olaparib, has been reported to protect against the LPS (Lipopolysaccharide)-induced acute lung and kidney injuries in a NF-κB-dependent manner in mice [49]. Numerous pre-clinical studies demonstrated that PARP1 inhibitors play an essential role in a range of inflammatory injuries and related diseases, especially the lung inflammatory disorders including ARDS (Acute Respiratory Distress Syndrome), COPD (Chronic Obstructive Pulmonary Disease) and asthma [40,46,50,51]. All these studies suggest that PARP1 inhibitors are of high relevance to the treatment of the novel pneumonia caused by SARS-CoV-2 infection, possibly via their roles in modulating inflammatory response.…”

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

“…Asthma is a complex, multifactorial disorder of lungs, mainly characterized by airway inflammation, immunoglobulin E (IgE) generation, and production of type 2 helper T cell (Th2) cytokines, namely IL‐4, IL‐5, and IL‐13 (comprehensively reviewed ). Repeated allergen exposure primarily results in accumulation of inflammatory cells mainly eosinophils, lymphocytes, and neutrophils in the lungs.…”

“…Poly(ADP‐ribose) polymerase (PARP; EC 2.4.2.30) is a family of nuclear enzymes consisting of 18 members that are primarily involved in DNA repair (comprehensively reviewed ). Indeed, PARP‐1 (an ambient member of the PARP family) is activated upon DNA damage and is reported to be engaged in various physiological functions such as chromatin remodeling, transcription, and regulation of inflammatory pathways .…”