PARP-1 inhibition ameliorates elastase induced lung inflammation and emphysema in mice

Dharwal, Vivek; Naura, Amarjit S.

doi:10.1016/j.bcp.2018.01.027

Cited by 49 publications

(38 citation statements)

References 88 publications

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“…In cancer, tumor-associated neutrophils are thought to contribute to inflammation in the tumor [51]. Of note, PARP-1 is important in the recruitment and function of neutrophils in different processes related to inflammation [52][53][54][55]. Meanwhile, the role of PARP-2 in neutrophil biology remains elusive (Figure 3).…”

Section: Role Of Parp-1 and Parp-2 In The Cellular Components Of The mentioning

confidence: 99%

“…These studies can provide information to rationalize the combined use of PARP inhibitors with other strategies aimed at reactivating the immune system against the tumor. Neutrophil function Impaired recruitment [52][53][54][55] Macrophage function Impaired recruitment Inhibition of LPS-induced pro-inflammatory genes [60] [63]…”

Section: Parp Inhibitors As Immunomodulatory Agentsmentioning

confidence: 99%

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Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies

Yélamos

Moreno-Lama

Jimeno

et al. 2020

Cancers

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Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 are enzymes which posttranslationally modify proteins through poly(ADP-ribosyl)ation (PARylation)-the transfer of ADP-ribose chains onto amino acid residues-with a resultant modulation of protein function. Many targets of PARP-1/2-dependent PARylation are involved in the DNA damage response and hence, the loss of these proteins disrupts a wide range of biological processes, from DNA repair and epigenetics to telomere and centromere regulation. The central role of these PARPs in DNA metabolism in cancer cells has led to the development of PARP inhibitors as new cancer therapeutics, both as adjuvant treatment potentiating chemo-, radio-, and immuno-therapies and as monotherapy exploiting cancer-specific defects in DNA repair. However, a cancer is not just made up of cancer cells and the tumor microenvironment also includes multiple other cell types, particularly stromal and immune cells. Interactions between these cells-cancerous and non-cancerous-are known to either favor or limit tumorigenesis. In recent years, an important role of PARP-1 and PARP-2 has been demonstrated in different aspects of the immune response, modulating both the innate and adaptive immune system. It is now emerging that PARP-1 and PARP-2 may not only impact cancer cell biology, but also modulate the anti-tumor immune response. Understanding the immunomodulatory roles of PARP-1 and PARP-2 may provide invaluable clues to the rational development of more selective PARP-centered therapies which target both the cancer and its microenvironment.

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Section: Role Of Parp-1 and Parp-2 In The Cellular Components Of The mentioning

confidence: 99%

Section: Parp Inhibitors As Immunomodulatory Agentsmentioning

confidence: 99%

Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies

Yélamos

Moreno-Lama

Jimeno

et al. 2020

Cancers

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“…Thus, COPD is associated with activation of systemic PARP 1 in peripheral blood lymphocytes [ 17 ] and the Ala allele polymorphism in the PARP1 gene is associated with a decreased risk of asthma [ 36 ]. Also, the PARP 1 inhibitor olaparib protects against various aspects of lung dysfunction in the elastase-induced mouse model of COPD [ 37 ].…”

Section: The Parpsmentioning

confidence: 99%

Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: starting with nicotinamide

Badawy

2020

Bioscience Reports

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COVID-19 induces a proinflammatory environment that is stronger in patients requiring intensive care. The cytokine components of this environment may determine efficacy or otherwise of glucocorticoid therapy. The immunity modulators, the aryl hydrocarbon receptor (AhR) and the nuclear NAD+-consuming enzyme poly (ADP-ribose) polymerase 1 (PARP 1) may play a critical role in COVID-19 pathophysiology. The AhR is over-expressed in coronaviruses, including COVID-19 and, as it regulates PARP gene expression, the latter is likely to be activated in COVID-19. PARP 1 activation leads to cell death mainly by depletion of NAD+ and ATP, especially when availability of these energy mediators is compromised. PARP expression is enhanced in other lung conditions: the pneumovirus respiratory syncytial virus (RSV) and chronic obstructive pulmonary disease (COPD). I propose that PARP 1 activation is the terminal point in a sequence of events culminating in patient mortality and should be the focus of COVID-19 immunotherapy. Potent PARP 1 inhibitors are undergoing trials in cancer, but a readily available inhibitor, nicotinamide, which possesses a highly desirable biochemical and activity profile, merits exploration. It conserves NAD+ and prevents ATP depletion by PARP 1 and Sirtuin 1 inhibition, enhances NAD+ synthesis, and hence that of NADP+ which is a stronger PARP inhibitor, reverses lung injury caused by ischaemia/reperfusion, inhibits proinflammatory cytokines, and is effective against HIV infection. These properties qualify nicotinamide for therapeutic use initially in conjunction with standard clinical care or combined with other agents, and subsequently as an adjunct to stronger PARP 1 inhibitors or other drugs.

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“…25 Cleaved PARP are required for cellular functions, such as production of inflammatory genes, and in response to TNF cytokines. 26 Hsp90 is a molecular chaperone that induces other molecules to fold properly, and to stabilize proteins for blocking heat stress, and it modulates a number of proteins necessary for cell growth. 27,28 Therefore, we reasoned that Hsp90 biomolecule may activate in F I G U R E 2 PCP inhibited hepatic Hsp90 expression in APAP-exposed liver cells.…”

Section: Discussionmentioning

confidence: 99%

Antihepatotoxic benefits of Poria cocos polysaccharides on acetaminophen‐lesioned livers in vivo and in vitro

Guo

Yang

et al. 2018

J of Cellular Biochemistry

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In our previous study, preliminary data indicates that Poria cocos polysaccharides (PCP) shows beneficial hepatoprotection against acetaminophen (APAP)‐induced liver injury in mice. However, biological molecular mechanism warrants to be further discussed. In current study, a number of biochemical tests and immunoassays were subjected to respective PCP‐dosed mice in vivo and liver cells in vitro. As a result, PCP‐treated mice showed reduced contents of inflammatory cytokines (tumor necrosis factor [TNF]‐β and TNFsR‐I), enzymological molecules (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase [LDL]), and heat shock protein 90 (Hsp90) after APAP exposure. Additionally, immunostaining assays exhibited that lowered‐positive cells of cleaved‐caspase‐3, cleaved‐poly ADP ribose polymerase, and Hsp90‐labeled cells in PCP‐treated livers were observed, and increased cluster of differentiation 29 (CD29), CD73‐positive cells in the spleen were detected. Further, PCP‐treated mouse liver cells resulted in increased cell growth, reduced LDL level. Increased proliferating cell nuclear antigen (PCNA), P38 mitogen‐activated protein kinase (MAPK)‐labeled cells and decreased Hsp90‐positive cells in APAP‐exposed liver cells were observed dose‐dependently after PCP cotreatments. Collectively, our present experimental findings elucidate that PCP beneficially play hepatoprotective effects against APAP‐lesioned liver cells in vivo and in vitro, potentially through the molecular mechanisms of suppressing cell death, reducing hepatocellular inflammatory stress and Hsp90 bioactivity.

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PARP-1 inhibition ameliorates elastase induced lung inflammation and emphysema in mice

Cited by 49 publications

References 88 publications

Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies

Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies

Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: starting with nicotinamide

Antihepatotoxic benefits of Poria cocos polysaccharides on acetaminophen‐lesioned livers in vivo and in vitro

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