Activation of human monocyte-derived macrophages by interferon γ is accompanied by increase of poly(ADP-ribose) polymerase activity

Berton, Giorgio; Sorio, Claudio; Laudanna, Carlo; Menegazzi, Marta; Prati, Alessandra Carcereri de; Suzuki, Hisanori

doi:10.1016/0167-4889(91)90228-p

Cited by 24 publications

(25 citation statements)

References 29 publications

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“…As for the decreased levels of PARP-1 in DCs exposed to LPS, we hypothesize that it could be due to as-yet unknown LPS-dependent specific signaling and/or PARP-1-dependent autorepression of its own promoter (55). Overall, these findings, along with evidence that PARP-1 activity is increased in IFN-␥-activated macrophages (8) and LPS-challenged microglia (7), suggest that induction of poly ADP-ribosylation plays a role in immune cell activation. This assumption is corroborated by our finding that chemical inhibition of PARP-1 affects the immunophenotype of DCs.…”

Section: Discussionsupporting

confidence: 56%

“…Specifically, the enzyme positively regulates activation of macrophages (8,9,35), microglia (7,36), granulocytes (37), lymphocytes (6,13,14), as well as TNF-␣-challenged endothelial cells (38). Also, parp-1 null mice are resistant to endotoxic shock (39), and PARP-1 inhibitors provide protection in models of pleuritis (40), arthritis (41), asthma (42), colitis (43,44), allergic encephalomyelitis (6,15,45), and other autoimmune disorders (46).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, numerous reports demonstrate that PARP-1 and PAR formation positively regulate transcription in several types of immune cells (4 -7), as well as macrophage activation (8,9), granulocyte migration (10,11), and T cell proliferation (6,12,13). Also, PARP-1 inhibition increases Ab class-switching (14), and alters Ab production during the autoimmune response in the CNS (15).…”

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confidence: 99%

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A Key Role for Poly(ADP-Ribose) Polymerase-1 Activity during Human Dendritic Cell Maturation

Aldinucci¹,

Gerlini

Fossati³

et al. 2007

The Journal of Immunology

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Poly(ADP-ribose) (PAR) polymerase (PARP)-1 is a nuclear enzyme regulating protein that functions by targeting PAR chains. Besides its classic role in DNA repair, PARP-1 is emerging as a key transcriptional regulator in different cell types including the immune ones. In this study, we investigated the role of PARP-1 in human dendritic cell (DC) function. We report that both PARP-1 mRNA and protein levels significantly increased during in vitro DC differentiation from monocytes. Of note, inhibitors of PARP-1 such as phenanthridinone and thieno[2,3-c]isoquinolin-5-one reduced expression of CD86 and CD83 in a concentration-dependent manner, having no effects on expression of CD80 and HLA-DR in mature DCs. In the same cultures, PARP-1 inhibitors also reduced production of IL-12 and IL-10. Addition of exogenous IL-12 to the culture medium partially restored CD86 expression in DCs exposed to PARP-1 inhibitors. In line with the role of PAR formation in NF-κB-dependent transactivation, we also report that phenanthridinone and thieno[2,3-c]isoquinolin-5-one impaired NF-κB and AP-1 subunit DNA binding activity in cellular extract of activated DCs. Finally, we show that PARP-1 inhibitors reduced the T cell allostimulatory activity of mature DCs, and that this reduction was prevented when DCs matured in the presence of PARP-1 inhibitors plus IL-12. Of note, nonproliferating T cells exposed to PARP-1 inhibitor-challenged DCs could undergo efficient proliferation when exposed to a subsequent activation stimulus such as anti-CD3 plus anti-CD-28. Together, data provide evidence for a key role of PARP-1 and poly ADP-ribosylation in DC immunocompetence and underscore the relevance of PARP-1 inhibitors to treatment of immune disorders.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Key Role for Poly(ADP-Ribose) Polymerase-1 Activity during Human Dendritic Cell Maturation

Aldinucci¹,

Gerlini

Fossati³

et al. 2007

The Journal of Immunology

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“…This was measured using methods described by Berton et al (1991). Tissues from control (groups 1 and 2) and sensitized, ovalbumin-challenged guinea pigs (group 3) were homogenized in 50 mM Tris HCI, pH 8, 4°C, containing 0.1% NP-40, 200 mM KCI, 2 mM MgCl 2 , 50 M ZnCl 2 , 2 mM dithiothreitol, and protease inhibitors (1 mM phenylmethylsulfonyl fluoride, 5 l/ml leupeptin, and antipain).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Poly(ADP-Ribose) Polymerase Prevents Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs

Suzuki¹,

Masini²,

Mazzocca³

et al. 2004

J Pharmacol Exp Ther

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Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in conditions associated with oxidative stress and inflammation. Because asthma is a chronic inflammatory disorder of the airways, we designed the present experimental study to evaluate the effects of PARP inhibition on allergeninduced asthma-like reaction in ovalbumin-sensitized guinea pigs. Cough and dyspnea in response to ovalbumin aerosol were absent in naive guinea pigs, whereas they became severe in the sensitized animals. In the latter ones, ovalbumin aerosol also induced a rapid increase in PARP activity, bronchiolar constriction, pulmonary air space inflation, mast cell degranulation, poly(ADP-ribose) and nitrotyrosine immunostaining, myeloperoxidase activity, and malondialdehyde in lung tissue, as well as a rise in the amounts of nitrites and tumor necrosis factor-␣ in bronchoalveolar lavage fluid. Pretreatment with the PARP inhibitors 3-aminobenzamide (10 mg/kg b.wt.) or 5-aminoisoquinolinone (0.5 mg/kg b.wt.) given i.p. 3 h before ovalbumin challenge significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both PARP inhibitors were also able to prevent the above morphological and biochemical changes of lung tissue or bronchoalveolar lavage fluid induced by ovalbumin challenge. Conversely, p-aminobenzoic acid, the inactive analog of 3-aminobenzamide, had no effects.Poly(ADP-ribose) polymerase (PARP; E.C.2.4.2.30) identifies a family of ubiquitous nuclear enzymes involved in many physiological and pathophysiological events, whose best studied member is PARP-1 (molecular mass 113 kDa) (Shieh et al

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“…However, growing evidence is revealing that polyADPribosylation also plays a key role in the regulation of gene transcription independently from DNA damage. Several reports demonstrated that PARP-1 regulates gene transcription in several types of immune cells (3), including dendritic cells (4) and macrophages (5). Inhibition of PARP-1 activity reduces the secretion of proinflammatory cytokines (3).…”

mentioning

confidence: 99%

Increased Foxp3+ Regulatory T Cells in Poly(ADP-Ribose) Polymerase-1 Deficiency

Nasta

Laudisi

Sambucci

et al. 2010

The Journal of Immunology

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Growing evidence is unveiling a role for poly(ADP-ribose) polymerase (PARP)-1 in the regulation of inflammatory/immune responses. In the current study, we investigated the effects of PARP-1 deficiency on regulatory T cell differentiation. Increased numbers of regulatory CD4+CD25+/Foxp3+ T cells were found in thymus, spleen, and lymph nodes of PARP-1 knockout (KO) mice compared with wild-type (WT) controls. The increased frequency of regulatory T cells in the periphery resulted in impaired CD4 cell proliferation and IL-2 production, which could be restored by CD25+ cell depletion. Phenotype and inhibitory functions of PARP-1 KO regulatory T cells were similar to WT cells, indicating that PARP-1 affects regulatory T cell differentiation rather than function. Purified naive CD4 cells from PARP-1 KO mice stimulated in vitro expressed forkhead box p3 mRNA at higher levels and generated a greater number of Foxp3+ cells (inducible regulatory T [iTreg] cells) than the WT counterpart. This finding was due to a higher rate of naive CD4 cell to Foxp3+ iTreg cell conversion rather than to higher resistance to apoptosis induction. Interestingly, PARP-1 deficiency did not affect retinoid-related orphan receptor-γt mRNA expression and differentiation of purified naive CD4 cells to Th17 cells. PARP-1 KO iTreg cells showed features similar to WT regulatory T cells, suggesting that modulation of PARP-1 during the immune response might be used to induce greater numbers of functional regulatory T cells. In conclusion, our findings represent the first evidence that PARP-1 can affect regulatory T cell differentiation and open new perspectives on potential targets for modulating immune responses.

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Activation of human monocyte-derived macrophages by interferon γ is accompanied by increase of poly(ADP-ribose) polymerase activity

Cited by 24 publications

References 29 publications

A Key Role for Poly(ADP-Ribose) Polymerase-1 Activity during Human Dendritic Cell Maturation

A Key Role for Poly(ADP-Ribose) Polymerase-1 Activity during Human Dendritic Cell Maturation

Inhibition of Poly(ADP-Ribose) Polymerase Prevents Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs

Increased Foxp3+ Regulatory T Cells in Poly(ADP-Ribose) Polymerase-1 Deficiency

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