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001-es BibID:	BIBFORM028555
Első szerző:	Haskó György (biokémikus)
Cím:	Ecto-5'-nucleotidase (CD73) decreases mortality and organ injury in sepsis / György Haskó, Balázs Csóka, Balázs Koscsó, Rachna Chandra, Pál Pacher, Linda F. Thompson, Edwin A. Deitch, Zoltán Spolarics, László Virág, Pál Gergely, Rolando H. Rolandelli, Zoltán H. Németh
Dátum:	2011
ISSN:	0022-1767
Megjegyzések:	The extracellular concentrations of adenosine are increased during sepsis, and adenosine receptors regulate the host's response to sepsis. In this study, we investigated the role of the adenosine-generating ectoenzyme, ecto-5'-nucleotidase (CD73), in regulating immune and organ function during sepsis. Polymicrobial sepsis was induced by subjecting CD73 knockout (KO) and wild type (WT) mice to cecal ligation and puncture. CD73 KO mice showed increased mortality in comparison with WT mice, which was associated with increased bacterial counts and elevated inflammatory cytokine and chemokine concentrations in the blood and peritoneum. CD73 deficiency promoted lung injury, as indicated by increased myeloperoxidase activity and neutrophil infiltration, and elevated pulmonary cytokine levels. CD73 KO mice had increased apoptosis in the thymus, as evidenced by increased cleavage of caspase-3 and poly(ADP-ribose) polymerase and increased activation of NF-B. Septic CD73 KO mice had higher blood urea nitrogen levels and increased cytokine levels in the kidney, indicating increased renal dysfunction. The increased kidney injury of CD73 KO mice was associated with augmented activation of p38 MAPK and decreased phosphorylation of Akt. Pharmacological inactivation of CD73 in WT mice using α, β-methylene ADP augmented cytokine levels in the blood and peritoneal lavage fluid. These findings suggest that CD73-derived adenosine may be beneficial in sepsis.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	Journal Of Immunology 187 : 8 (2011), p. 4256-4267. -
További szerzők:	Csóka Balázs (1975-) (biokémikus) Koscsó Balázs Chandra, Rachna Pacher Pál Thompson, Linda F. Deitch, Edwin A. Spolarics Zoltán Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Gergely Pál (1947-) (biokémikus) Rolandelli, Rolando H. Németh Zoltán H.
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001-es BibID:	BIBFORM028557
Első szerző:	Koscsó Balázs
Cím:	Adenosine Augments IL-10 Production by Microglial Cells through an A2B Adenosine Receptor-Mediated Process / Balázs Koscsó, Balázs Csóka, Zsolt Selmeczy, Leonóra Himer, Pál Pacher, László Virág, György Haskó
Dátum:	2012
ISSN:	0022-1767
Megjegyzések:	Microglia are activated by pathogen-associated molecular patterns and produce proinflammatory cytokines, such as TNF-alfa, IL-6, and IL-12, and the anti-inflammatory cytokine IL-10. Adenosine is an endogenous purine nucleoside and a ligand of four G protein-coupled adenosine receptors (ARs), which are the A(1)AR, A(2A)AR, A(2B)AR, and A(3)AR. ARs have been shown to suppress TNF-alfa production by microglia, but their role in regulating IL-10 production has not been studied. In this study, we demonstrate that adenosine augments IL-10 production by activated murine microglia while suppressing the production of proinflammatory cytokines. Because the order of potency of selective AR agonists in inducing IL-10 production was NECA > IB-MECA > CCPA > CGS21680, and the A(2B)AR antagonist MRS1754 prevented the effect of NECA, we conclude that the stimulatory effect of adenosine on IL-10 production is mediated by the A(2B)AR. Mechanistically, adenosine augmented IL-10 mRNA accumulation by a transcriptional process. Using mutant IL-10 promoter constructs we showed that a CREB-binding region in the promoter mediated the augmenting effect of adenosine on IL-10 transcription. Chromatin immunoprecipitation analysis demonstrated that adenosine induced CREB phosphorylation at the IL-10 promoter. Silencing CREB using lentivirally delivered short hairpin RNA blocked the enhancing effect of adenosine on IL-10 production, confirming a role for CREB in mediating the stimulatory effect of adenosine on IL-10 production. In addition, adenosine augmented IL-10 production by stimulating p38 MAPK. Collectively, our results establish that A(2B)ARs augment IL-10 production by activated murine microglia.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	Journal of Immunology 188 : 1 (2012), p. 445-453. -
További szerzők:	Csóka Balázs (1975-) (biokémikus) Selmeczy Zsolt Himer Leonóra Pacher Pál Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Haskó György (1967-) (biokémikus)
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001-es BibID:	BIBFORM008295
Első szerző:	Tóth Beáta
Cím:	Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells / Beáta Tóth, Éva Garabuczi, Zsolt Sarang, György Vereb, György Vámosi, Daniel Aeschlimann, Bernadett Blaskó, Bálint Bécsi, Ferenc Erdődi, Adam Lacy-Hulbert, Ailiang Zhang, Laura Falsca, Raymond B. Birge, Zoltán Balajthy, Gerry Melino, László Fésüs, Zsuzsa Szondy
Dátum:	2009
Megjegyzések:	Transglutaminase 2 (TG2), a protein cross-linking enzyme with many additional biological functions, acts as coreceptor for integrin beta3. We have previously shown that TG2-/- mice develop an age-dependent autoimmunity due to defective in vivo clearance of apoptotic cells. Here we report that TG2 on the cell surface and in guanine nucleotide-bound form promotes phagocytosis. Besides being a binding partner for integrin beta3, a receptor known to mediate the uptake of apoptotic cells via activating Rac1, we also show that TG2 binds MFG-E8 (milk fat globulin EGF factor 8), a protein known to bridge integrin beta3 to apoptotic cells. Finally, we report that in wild-type macrophages one or two engulfing portals are formed during phagocytosis of apoptotic cells that are characterized by accumulation of integrin beta3 and Rac1. In the absence of TG2, integrin beta3 cannot properly recognize the apoptotic cells, is not accumulated in the phagocytic cup, and its signaling is impaired. As a result, the formation of the engulfing portals, as well as the portals formed, is much less efficient. We propose that TG2 has a novel function to stabilize efficient phagocytic portals.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	The Journal of Immunology 182 : 4 (2009), p. 2084-2092. -
További szerzők:	Garabuczi Éva (1982-) (biokémikus, molekuláris biológus) Sarang Zsolt (1976-) (mikrobiológus) Vereb György (1965-) (biofizikus, orvos) Vámosi György (1967-) (biofizikus) Aeschlimann, Daniel Blaskó Bernadett Bécsi Bálint (1981-) (vegyészmérnök) Erdődi Ferenc (1953-) (biokémikus) Lacy-Hulbert, Adam Zhang, Ailiang Falsca, Laura Birge, Raymond B. Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Melino, Gerry Fésüs László (1947-) (orvos biokémikus) Szondy Zsuzsanna (1959-) (molekuláris sejtbiológus, biokémikus)
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001-es BibID:	BIBFORM028439
Első szerző:	Virág László (biokémikus, sejtbiológus, farmakológus)
Cím:	Poly(ADP-ribose) synthetase activation mediates mitochondrial injury during oxidant-induced cell death / László Virág, Andrew L. Salzman, Csaba Szabó
Dátum:	1998
ISSN:	1550-6606
Megjegyzések:	Reactive oxidant species are important mediators of tissue injury in shock, inflammation, and reperfusion injury. The actions of a number of these oxidants (e.g., hydroxyl radical and peroxynitrite, a reactive oxidant produced by the reaction of nitric oxide and superoxide) are mediated in part by the activation of the nuclear nick sensor enzyme, poly(ADP)-ribose synthetase (PARS), with consequent cellular energy depletion. Here we investigated whether PARS activation contributes to the mitochondrial alterations in cells exposed to oxidants. Authentic peroxynitrite (20 microM), the peroxynitrite-generating compound 3-morpholinosidnonimine, the combination of pyrogallol and S-nitroso-N-acetyl-D,L-penicillamine, as well as hydrogen peroxide induced a time- and dose-dependent decrease in mitochondrial transmembrane potential (delta psi(m)) in thymocytes, as determined by flow cytometry using the mitochondrial potential sensitive dyes DiOC6(3) and JC-1. A time- and dose-dependent increase in secondary reactive oxygen intermediate production and loss of cardiolipin, an indicator of mitochondrial membrane damage, were also observed, as measured by flow cytometry using the fluorescent dyes dihydroethidine and nonyl-acridine orange, respectively. Inhibition of PARS by 3-aminobenzamide or 5-iodo-6-amino-1,2-benzopyrone attenuated peroxynitrite-induced delta psi(m) reduction, secondary reactive oxygen intermediate generation, cardiolipin degradation, and intracellular calcium mobilization. Furthermore, thymocytes from PARS-deficient animals were protected against the peroxynitrite- and hydrogen peroxide-induced functional and ultrastructural mitochondrial alterations. In conclusion, mitochondrial perturbations during oxidant-mediated cytotoxicity are, to a significant degree, related to PARS activation rather than to direct effects of the oxidants on the mitochondria.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	Journal of Immunology. - 161 : 7 (1998), p. 3753-3759. -
További szerzők:	Salzman, Andrew L. Szabó Csaba (1967-) (orvos)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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