Treatment with a novel poly(ADP-ribose) glycohydrolase inhibitor reduces development of septic shock-like syndrome induced by zymosan in mice

Genovese, Tiziana; Paola, Rosanna Di; Catalano, Paolo N.; Li, Jia He; Xu, Weizheng; Massuda, Edmond; Caputi, Achille P.; Zhang, Jie; Cuzzocrea, Salvatore

doi:10.1097/01.ccm.0000127775.70867.0c

Cited by 53 publications

(33 citation statements)

References 29 publications

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“…Some of them have already been shown to associate with inflammatory pathologies: such as PARP-2 (reviewed in [35]), PARP-3 [36], tankyrases [79], or PARP-14 [30,31]. Moreover, poly(ADP-ribose) glycohydrolase has been implicated in the regulation of immune functions [80,81] underlining the central role of poly(ADP-ribosyl)ation in inflammation. A key question is whether the powerful anti-inflammatory effects of PARP inhibitors as observed in animal models can be translated to human diseases and to determine the risk benefit ratio of acute and chronic administration of PARP inhibitors in non-cancer patients.…”

Section: Resultsmentioning

confidence: 99%

Role of poly(ADP‐ribose) polymerases in the regulation of inflammatory processes

Bai

Virág

2012

FEBS Letters

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a b s t r a c t PARP enzymes influence the immune system at several key points and thus modulate inflammatory diseases. PARP enzymes affect immune cell maturation and differentiation and regulate the expression of inflammatory mediators such as cytokines, chemokines, inducible nitric oxide synthase and adhesion molecules. Moreover, PARP enzymes are key regulators of cell death during inflammationrelated oxidative and nitrosative stress. Here we provide an overview of the different inflammatory diseases regulated by PARP enzymes.

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Section: Resultsmentioning

confidence: 99%

Role of poly(ADP‐ribose) polymerases in the regulation of inflammatory processes

Bai

Virág

2012

FEBS Letters

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“…Based on the known PARG inhibitory effect of gallotannin and the antiinflammatory effect of a recently developed nontannin PARG inhibitor (Genovese et al, 2004), we have also investigated the effect of GT on poly(ADP-ribose) metabolism as a possible mechanism underlying the anti-inflammatory effect of GT. Treatment of the cells with the cytokines for various time Fig.…”

Section: Gallotannin Inhibits Cytokine and Chemokine Expression 899mentioning

confidence: 99%

Gallotannin Inhibits the Expression of Chemokines and Inflammatory Cytokines in A549 Cells

Erdélyi¹,

Kiss²,

Bakondi³

et al. 2005

Mol Pharmacol

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Tannins are plant-derived water-soluble polyphenols with wideranging biological activities. The mechanisms underlying the anti-inflammatory effect of tannins are not fully understood and may be the result of inhibition of poly(ADP-ribose) (PAR) glycohydrolase (PARG), the main catabolic enzyme of PAR metabolism. Therefore, we set out to investigate the mechanism of the anti-inflammatory effect of gallotannin (GT) in A549 cells with special regard to the role of poly(ADP-ribosyl)ation. Using an inflammation-focused low-density array and reverse transcription-polymerase chain reaction, we found that GT suppressed the expression of most cytokines and chemokines in cytokine-stimulated A549 cells, whereas the PARP inhibitor PJ-34 only inhibited few transcripts. Activation of the transcription factors, nuclear factor B (NF-B) and activator protein 1 (AP-1), was blocked by GT, whereas PJ-34 only suppressed NF-B activation but not AP-1 activation. GT also inhibited IB phosphorylation and nuclear translocation of NF-B, but PJ-34 had no effect on these upstream events. In the AP-1 pathway, GT treatment, even in the absence of cytokines, caused maximal phosphorylation of c-Jun N-terminal kinase and c-Jun. GT also caused a low-level phosphorylation of p38, extracellular signal-regulated kinases 1 and 2, activating transcription factor2, and cAMP-response element-binding protein but inhibited cytokine-induced phosphorylation of these kinases and transcription factors. GT inhibited protein phosphatases 1 and 2A, which may explain the increased phosphorylation of mitogenactivated protein kinase and their substrates. GT exerted potent antioxidant effect but failed to cause PAR accumulation. In summary, the potent inhibitory effects of GT on the transcription of cytokine and chemokine genes are probably not related to PARG inhibition. Inhibition of AP-1 activation and upstream signaling events may be responsible for the effects of GT.Tannins are water-soluble polyphenols that are widely distributed in the plant kingdom, including food grains and fruits. So far, more than a thousand different tannins have been characterized and ordered into four major groups: 1) gallotannins (GT), 2) ellagitannins, 3) complex, and 4) condensed tannins, with gallotannins and ellagitannins considered the most widespread types. The common structural elements of all tannins include one or more polyol units (mostly D-glucose) and one or more polyphenols (gallic acid, 3,4,5-trihydroxyl benzoic acid).The simplest hydrolyzable tannin, gallotannin, is a mixture of polygalloyl esthers of glucose. Gallotannin and other tannins have been shown to exert various biological effects ranging from anti-inflammatory to anticancer and antiviral effects (Fong et al., 1972;Mota et al., 1985;Uchiumi et al., 1996;Van Molle et al., 2000;Feldman et al., 2001). The mechanisms underlying the anti-inflammatory effect of tannins include the scavenging of radicals (antioxidant effect) (Hagerman et al., 1999) and inhibition of the expression of

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“…In vivo validation on the interaction of the CD5 ectodomain with fungal constituents was obtained from the mouse model of septic shock-like syndrome induced by zymosan (26). In this model, administration of a single dose of zymosan (500 mg/kg, i.p.)…”

Section: The Soluble Cd5 Ectodomain Protects From Zymosan-induced Septicmentioning

confidence: 99%

The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome

Vera

Fenutría

Cañadas

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

122

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The CD5 lymphocyte surface receptor is a group B member of the ancient and highly conserved scavenger receptor cysteine-rich superfamily. CD5 is expressed on mature T and B1a cells, where it is known to modulate lymphocyte activation and/or differentiation processes. Recently, the interaction of a few group B SRCR members (CD6, Sp␣, and DMBT1) with conserved microbial structures has been reported.

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Treatment with a novel poly(ADP-ribose) glycohydrolase inhibitor reduces development of septic shock-like syndrome induced by zymosan in mice

Cited by 53 publications

References 29 publications

Role of poly(ADP‐ribose) polymerases in the regulation of inflammatory processes

Role of poly(ADP‐ribose) polymerases in the regulation of inflammatory processes

Gallotannin Inhibits the Expression of Chemokines and Inflammatory Cytokines in A549 Cells

The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome

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