2,3,7,8-tetrachlorodibenzo-p-dioxin and the viral infection

Fiorito, Filomena; Santamaria, Rita; Irace, Carlo; Martino, Luisa De; Iovane, G.

doi:10.1016/j.envres.2016.11.004

Cited by 24 publications

(38 citation statements)

References 92 publications

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“…Forced expression of the Bcl-2 gene attenuated TCDD-caused apoptosis of HUVECs, along with suppression of caspase 3 activity. In agreement with our observations, TCDD also promotes apoptosis of human trophoblast-like JAR cells [53] and bovine MDBK cells [54] by down-regulating expression of the Bcl-2 gene. Given that EP3 inhibition or knockdown restored TCDD-caused-p38 MAPK activation and suppressed Bcl-2 expression, EP3-mediated activation of the p38MAPK/Bcl-2 pathway contributes to apoptosis increased by TCDD in HUVECs.…”

Section: Discussionsupporting

confidence: 93%

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl‐2 pathway

Liu

Guo

et al. 2017

J Cellular Molecular Medi

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Endothelial injury or dysfunction is an early event in the pathogenesis of atherosclerosis. Epidemiological and animal studies have shown that 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin (TCDD) exposure increases morbidity and mortality from chronic cardiovascular diseases, including atherosclerosis. However, whether or how TCDD exposure causes endothelial injury or dysfunction remains largely unknown. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to different doses of TCDD, and cell apoptosis was examined. We found that TCDD treatment increased caspase 3 activity and apoptosis in HUVECs in a dose‐dependent manner,at doses from 10 to 40 nM. TCDD increased cyclooxygenase enzymes (COX)‐2 expression and its downstream prostaglandin (PG) production (mainly PGE2 and 6‐keto‐PGF1α) in HUVECs. Interestingly, inhibition of COX‐2, but not COX‐1, markedly attenuated TCDD‐triggered apoptosis in HUVECs. Pharmacological inhibition or gene silencing of the PGE2 receptor subtype 3 (EP3) suppressed the augmented apoptosis in TCDD‐treated HUVECs. Activation of the EP3 receptor enhanced p38 MAPK phosphorylation and decreased Bcl‐2 expression following TCDD treatment. Both p38 MAPK suppression and Bcl‐2 overexpression attenuated the apoptosis in TCDD‐treated HUVECs. TCDD increased EP3‐dependent Rho activity and subsequently promoted p38MAPK/Bcl‐2 pathway‐mediated apoptosis in HUVECs. In addition, TCDD promoted apoptosis in vascular endothelium and delayed re‐endothelialization after femoral artery injury in wild‐type (WT) mice, but not in EP3−/− mice. In summary, TCDD promotes endothelial apoptosis through the COX‐2/PGE2/EP3/p38MAPK/Bcl‐2 pathway. Given the cardiovascular hazard of a COX‐2 inhibitor, our findings indicate that the EP3 receptor and its downstream pathways may be potential targets for prevention of TCDD‐associated cardiovascular diseases.

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Section: Discussionsupporting

confidence: 93%

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl‐2 pathway

Liu

Guo

et al. 2017

J Cellular Molecular Medi

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“…In particular, analysis of apoptotic pathway showed the activation of both examined caspases and the PARP cleavage (Fig. 3 ), according to previous studies 4 , 6 , 8 – 11 . MG-132 completely inhibited BoHV-1-induced apoptosis, by blocking the activation of initiator caspase 9, as well as, of executioner caspase 3, and no cleavage of PARP was observed (Fig.…”

Section: Discussionsupporting

confidence: 83%

MG-132 reduces virus release in Bovine herpesvirus-1 infection

Fiorito

Iovane

Cantiello

et al. 2017

Sci Rep

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Bovine herpesvirus 1 (BoHV-1) can provoke conjunctivitis, abortions and shipping fever. BoHV-1 infection can also cause immunosuppression and increased susceptibility to secondary bacterial infections, leading to pneumonia and occasionally to death. Herein, we investigated the influence of MG-132, a proteasome inhibitor, on BoHV-1 infection in bovine kidney (MDBK) cells. Infection of MDBK cells with BoHV-1 induces apoptotic cell death that enhances virus release. Whereas, MG-132 inhibited virus-induced apoptosis and stimulated autophagy. Protein expression of viral infected cell protein 0 (bICP0), which is constitutively expressed during infection and is able to stimulate Nuclear factor kappa B (NF-κB), was completely inhibited by MG-132. These results were accompanied by a significant delay in the NF-κB activation. Interestingly, the efficient virus release provoked by BoHV-1-induced apoptosis was significantly reduced by MG-132. Overall, this study suggests that MG-132, through the activation of autophagy, may limit BoHV-1 replication during productive infection, by providing an antiviral defense mechanism.

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“…In HCV infection, the AhR-CYP1A1 (cytochrome p450 1A1) pathway is upregulated, resulting in the accumulation of enlarged lipid droplets which enhance the virus assembly; and AHR inhibitors reduce the production of infectious virions (50). In HIV-1 infection, AHR activation stimulated by ligand of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or by TCDD chemical homologue 3-methylcholanthrene (3-MC) was previously shown to reactivate HIV-1 from latency (51–54), and induction of AHR and AHR-regulated CYP1A1 enzymes by TCDD was shown to be associated with enhanced activity of HIV RNA-dependent DNA polymerase (Pol) and increased expression of viral protein in human T cells (55). Also, AHR-regulated CYP1A1 activation, induced by polycyclic aromatic hydrocarbons (PAH), a major constituent of cigarette smoke, has been implicated in HIV pathogenesis and disease progression (56).…”

Section: Introductionmentioning

confidence: 99%

Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation

Sun

et al. 2019

mBio

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Cellular metabolic pathways that are altered by HIV-1 infection may accelerate disease progression. Dysfunction in tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the mechanism responsible was not known. This study demonstrates that Trp metabolites augment the activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, to promote HIV-1 infection and transcription. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection.

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2,3,7,8-tetrachlorodibenzo-p-dioxin and the viral infection

Cited by 24 publications

References 92 publications

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl‐2 pathway

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl‐2 pathway

MG-132 reduces virus release in Bovine herpesvirus-1 infection

Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation

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