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.

Highlights

  • Pulmonary inflammatory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and acute lung injury (ALI) constitute a huge socio-economic burden on present society

  • We extended our findings by stimulating the T-cell receptor (TCR) of CD4+ T cells derived from humans and our data confirm that PARP-1 inhibition suppresses the production of Th2 cytokines and expression of GATA-3 in cells of human origin [74]

  • Despite the fact that PARP-1 has been reported to play a role in activator protein 1 (AP-1) activation in several inflammatory disorders, including ALI [144,145,146], we could not find any study in literature addressing the PARP and AP-1 interrelationship in asthma

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Summary

Introduction

Pulmonary inflammatory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and acute lung injury (ALI) constitute a huge socio-economic burden on present society. Zaffini et al evaluated the therapeutic effects of PARP-1 inhibition on airway inflammation and remodeling using HDM-induced mouse model of chronic asthma (established by challenging the mice for 5 days/week for five consecutive weeks).

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