Cytokine gene expression in human cardiac allograft recipients

Wu, Catherine J.; Kurbegov, Dax; Lattin, Brandon; Burchard, Esteban G.; Finkle, Carolyn; Valantine, Hannah A.; Billingham, Margaret E.; Starnes, Vaughn A.; Clayberger, Carol

doi:10.1016/0966-3274(94)90061-2

Cited by 25 publications

(12 citation statements)

References 36 publications

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“…Proinflammatory cytokines mediate inflammatory and immune responses during ischemia-reperfusion injury and early rejection after heart transplantation in humans [1,2]. Interleukin-17 (IL-17) is a potent proinflammatory cytokine originally referred to as cytotoxic T lymphocyte-associated serine esterase-8 (CTLA-8) [3].…”

Section: Introductionmentioning

confidence: 99%

Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model☆

Simeoni

Fleury

et al. 2006

European Journal of Cardio-Thoracic Surgery

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Section: Introductionmentioning

confidence: 99%

Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model☆

Simeoni

Fleury

et al. 2006

European Journal of Cardio-Thoracic Surgery

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“…iNOS is strongly induced in cardiac myocytes exposed to macrophage-derived cytokines, including tumor necrosis factor (TNF)-␣, interferon (IFN)-␥, and interleukin (IL)-1␤, 10,12,14 -18 and during allograft rejection, in which cytokines are present in high levels. 19 This strong induction may be attributed to the presence of more than 22 immune effector-responsive elements in the iNOS promoter, including binding sites for nuclear factor B and IFN regulatory factor-1. 20 The high levels of NO produced by iNOS are cytotoxic and are an important part of the host defense against microbial invasion in many species.…”

mentioning

confidence: 99%

Modulation of Cytokine-Induced Cardiac Myocyte Apoptosis by Nitric Oxide, Bak, and Bcl-x

Ing

Zang

Dzau

et al. 1999

Circulation Research

258

148

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Abstract-Cytokine-induced NO production depresses myocardial contractility and has been shown to be cytotoxic to cardiac myocytes. However, the mechanisms of cytokine-induced cardiac myocyte cell death are unclear. To analyze these mechanisms in detail, we treated neonatal cardiac myocytes in serum-free culture with a combination of the macrophage-derived cytokines interleukin-1␤, tumor necrosis factor-␣, and interferon-␥. These cytokines caused a time-dependent induction of cardiac myocyte apoptosis, but not necrosis, beginning 72 hours after treatment, as determined by nuclear morphology, DNA internucleosomal cleavage, and cleavage of poly(ADP-ribose) polymerase, reflecting caspase activation. Apoptosis was preceded by a Ͼ50-fold induction of inducible NO synthase mRNA and the release of large amounts (5 to 8 nmol/g protein) of NO metabolites (NOx) into the medium. Cell death was completely blocked by an NO synthase inhibitor and attenuated by antioxidants (N-acetylcysteine and DTT) and the caspase inhibitor ZVAD-fmk. Cytokines also mediated an NO-dependent, sustained increase in myocyte expression of the Bcl-2 homologs Bak and Bcl-x(L). The NO donor S-nitrosoglutathione also induced apoptosis and cell levels of Bak, but not of Bcl-x(L). All effects of cytokines, including poly(ADP-ribose) polymerase cleavage, could be attributed to interleukin-1␤; interferon-␥ and tumor necrosis factor-␣ had no independent effects on apoptosis or on NOx production. We conclude that cytokine toxicity to neonatal cardiac myocytes results from the induction of NO and subsequent activation of apoptosis, at least in part through the generation of oxygen free radicals. The rate and extent of this apoptosis is modulated by alterations in the cellular balance of Bak and Bcl-x(L), which respond differentially to cytokine-induced and exogenous NO and by the availability of oxidant species. (Circ Res. 1999;84:21-33.)Key Words: poly(ADP-ribose) polymerase Ⅲ protein kinase G Ⅲ nitric oxide Ⅲ Bcl-x(L) Ⅲ oxidative stress

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“…26 Experimental studies are necessary to reveal the intracellular distribution of ubiquitin mediated by Apollon and its possible role in inflammation associated with ACR. 12,13,38,39 …”

Section: Discussionmentioning

confidence: 98%