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001-es BibID:	BIBFORM072211
035-os BibID:	(cikkazonosító)4310816 (PMID)29743981 (PMCID)PMC5883980
Első szerző:	Erdei Judit Zsuzsa (vegyész)
Cím:	Induction Of NLRP3 Inflammasome Activation By Heme In Human Endothelial Cells / Judit Erdei, Andrea Tóth, Enikő Balogh, Benard Bogonko Nyakundi, Emese Bányai, Bernhard Ryffel, György Paragh, Mario D. Cordero, Viktória Jeney
Dátum:	2018
ISSN:	1942-0994 1942-0900
Megjegyzések:	Hemolytic or hemorrhagic episodes are often associated with inflammation even when infectious agents are absent suggesting that red blood cells (RBCs) release damage-associated molecular patterns (DAMPs). DAMPs activate immune and nonimmune cells through pattern recognition receptors. Heme, released from RBCs, is a DAMP and induces IL-1β production through the activation of the nucleotide-binding domain and leucine-rich repeat-containing family and pyrin domain containing 3 (NLRP3) in macrophages; however, other cellular targets of heme-mediated inflammasome activation were not investigated. Because of their location, endothelial cells can be largely exposed to RBC-derived DAMPs; therefore, we investigated whether heme and other hemoglobin- (Hb-) derived species induce NLRP3 inflammasome activation in these cells. We found that heme upregulated NLRP3 expression and induced active IL-1β production in human umbilical vein endothelial cells (HUVECs). LPS priming largely amplified the heme-mediated production of IL-1β. Heme administration into C57BL/6 mice induced caspase-1 activation and cleavage of IL-1β which was not observed in NLRP3?/? mice. Unfettered production of reactive oxygen species played a critical role in heme-mediated NLRP3 activation. Activation of NLRP3 by heme required structural integrity of the heme molecule, as neither protoporphyrin IX nor iron-induced IL-1β production. Neither naive nor oxidized forms of Hb were able to induce IL-1β production in HUVECs. Our results identified endothelial cells as a target of heme-mediated NLRP3 activation that can contribute to the inflammation triggered by sterile hemolysis. Thus, understanding the characteristics and cellular counterparts of RBC-derived DAMPs might allow us to identify new therapeutic targets for hemolytic diseases.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Heme endothelial cells hemolysis hemoglobin DAMP NLRP3 inflammasome activation IL-1? ROS
Megjelenés:	Oxidative Medicine and Cellular Longevity. - 2018 (2018), p. 1-14. -
További szerzők:	Tóth Andrea (1992-) (molekuláris biológus) Balogh Enikő (1987-) (molekuláris biológus) Nyakundi, Benard Bogonko (1983-) (biokémikus) Bányai Emese (1984-) (orvos) Ryffel, Bernhard Paragh György (1953-) (belgyógyász) Cordero, Mario D. Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:	NKFIH K116024 Egyéb GINOP-2.3.2-15-2016-00005 GINOP
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001-es BibID:	BIBFORM102500
035-os BibID:	(cikkazonosító)3600 (scopus)85126835884 (wos)000781089600001
Első szerző:	Lima, Carla
Cím:	Natterin-Induced Neutrophilia Is Dependent on cGAS/STING Activation via Type I IFN Signaling Pathway / Lima Carla, Andrade-Barros Aline Ingrid, Bernardo Jefferson Thiago Gonçalves, Balogh Eniko, Quesniaux Valerie F., Ryffel Bernhard, Lopes-Ferreira Monica
Dátum:	2022
ISSN:	1661-6596 1422-0067
Megjegyzések:	Natterin is a potent pro-inflammatory fish molecule, inducing local and systemic IL-1?/IL-1R1-dependent neutrophilia mediated by non-canonical NLRP6 and NLRC4 inflammasome activation in mice, independent of NLRP3. In this work, we investigated whether Natterin activates mitochondrial damage, resulting in self-DNA leaks into the cytosol, and whether the DNA sensor cGAS and STING pathway participate in triggering the innate immune response. Employing a peritonitis mouse model, we found that the deficiency of the tlr2/tlr4, myd88 and trif results in decreased neutrophil influx to peritoneal cavities of mice, indicative that in addition to MyD88, TRIF contributes to neutrophilia triggered by TLR4 engagement by Natterin. Next, we demonstrated that gpcr91 deficiency in mice abolished the neutrophil recruitment after Natterin injection, but mice pre-treated with 2-deoxy-d-glucose that blocks glycolysis presented similar infiltration than WT Natterin-injected mice. In addition, we observed that, compared with the WT Natterin-injected mice, DPI and cyclosporin A treated mice had a lower number of neutrophils in the peritoneal exudate. The levels of dsDNA in the supernatant of the peritoneal exudate and processed IL-33 in the supernatant of the peritoneal exudate or cytoplasmic supernatant of the peritoneal cell lysate of WT Natterin-injected mice were several folds higher than those of the control mice. The recruitment of neutrophils to peritoneal cavity 2 h post-Natterin injection was intensely impaired in ifnar KO mice and partially in il-28r KO mice, but not in ifn?r KO mice. Finally, using cgas KO, sting KO, or irf3 KO mice we found that recruitment of neutrophils to peritoneal cavities was virtually abolished in response to Natterin. These findings reveal cytosolic DNA sensors as critical regulators for Natterin-induced neutrophilia.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Natterin neutrophilia self-DNA cGAS/STING/IRF3 pathway type I IFN signaling
Megjelenés:	International Journal Of Molecular Sciences. - 23 : 7 (2022), p. 1-15. -
További szerzők:	Andrade-Barros, Aline Ingrid Bernardo, Jefferson Thiago Gonçalves Balogh Enikő (1987-) (molekuláris biológus) Quesniaux, Valerie F. Ryffel, Bernhard Lopes-Ferreira, Monica
Pályázati támogatás:	FAPESP 2021/06084-8 Egyéb FAPESP 2019/10500-7 Egyéb FAPESP 2018/17413-0 Egyéb FAPESP 2013/07467-1 Egyéb FEDER EX016008 TARGET-Ex Egyéb FEDER EX010381 EURo-FéRI Egyéb
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001-es BibID:	BIBFORM091958
035-os BibID:	(cikkazonosító)107287
Első szerző:	Lima, Carla
Cím:	Natterin an aerolysin-like fish toxin drives IL-1[beta]-dependent neutrophilic inflammation mediated by caspase-1 and caspase-11 activated by the inflammasome sensor NLRP6 / Lima Carla, Falcao Maria Alice Pimentel, Andrade-Barros Aline Ingrid, Seni-Silva Ana Carolina, Grund Lidiane Zito, Balogh Eniko, Conceicao Katia, Queniaux Valerie F., Ryffel Bernhard, Lopes-Ferreira Monica
Dátum:	2021
ISSN:	1567-5769
Megjegyzések:	Natterin is an aerolysin-like pore-forming toxin responsible for the toxic effects of the venom of the medically significant fish Thalassophryne nattereri. Using a combination of pharmacologic and genetic loss-of-function approaches we conduct a systematic investigation of the regulatory mechanisms that control Natterin-induced neutrophilic inflammation in the peritonitis model. Our data confirmed the capacity of Natterin to induce a strong and sustained neutrophilic inflammation leading to systemic inflammatory lung infiltration and revealed overlapping regulatory paths in its control. We found that Natterin induced the extracellular release of mature IL-1? and the sustained production of IL-33 by bronchial epithelial cells. We confirmed the dependence of both ST2/IL-33 and IL-17A/IL-17RA signaling on the local and systemic neutrophils migration, as well as the crucial role of IL-1?, caspase-1 and caspase-11 for neutrophilic inflammation. The inflammation triggered by Natterin was a gasdermin-D-dependent inflammasome process, despite the cells did not die by pyroptosis. Finally, neutrophilic inflammation was mediated by non-canonical NLRP6 and NLRC4 adaptors through ASC interaction, independent of NLRP3. Our data highlight that the inflammatory process dependent on non-canonical inflammasome activation can be a target for pharmacological intervention in accidents by T. nattereri, which does not have adequate specific therapy.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	International Immunopharmacology. - 91 (2021), p. 1-12. -
További szerzők:	Falcao, Maria Alice Pimentel Andrade-Barros, Aline Ingrid Seni-Silva, Ana Carolina Grund, Lidiane Zito Balogh Enikő (1987-) (molekuláris biológus) Conceiçao, Katia Queniaux, Valerie F. Ryffel, Bernhard Lopes-Ferreira, Monica
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001-es BibID:	BIBFORM078435
035-os BibID:	(PMID)30389578
Első szerző:	Nyakundi, Benard Bogonko (biokémikus)
Cím:	Oxidized hemoglobin forms contribute to NLRP3 inflammasome-driven IL1[beta] production upon intravascular hemolysis / Benard Bogonko Nyakundi, Andrea Tóth, Enikő Balogh, Béla Nagy, Judit Erdei, Bernhard Ryffel, György Paragh, Mario D. Cordero, Viktória Jeney
Dátum:	2019
Megjegyzések:	Damage associated molecular patterns (DAMPs) are released form red blood cells (RBCs) during intravascular hemolysis (IVH). Extracellular heme, with its pro-oxidant, pro-inflammatory and cytotoxic effects, is sensed by innate immune cells through pattern recognition receptors such as toll-like receptor 4 and nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3), while free availability of heme is strictly controlled. Here we investigated the involvement of different hemoglobin (Hb) forms in hemolysis-associated inflammatory responses. We found that after IVH most of the extracellular heme molecules are localized in oxidized Hb forms. IVH was associated with caspase-1 activation and formation of mature IL-1β in plasma and in the liver of C57BL/6 mice. We showed that ferrylHb (FHb) induces active IL-1β production in LPS-primed macrophages in vitro and triggered intraperitoneal recruitment of neutrophils and monocytes, caspase-1 activation and active IL-1β formation in the liver of C57BL/6 mice. NLRP3 deficiency provided a survival advantage upon IVH, without influencing the extent of RBC lysis or the accumulation of oxidized Hb forms. However, both hemolysis-induced and FHb-induced pro-inflammatory responses were largely attenuated in Nlrp3-/- mice. Taken together, FHb is a potent trigger of NLRP3 activation and production of IL-1β in vitro and in vivo, suggesting that FHb may contribute to hemolysis-induced inflammation. Identification of RBC-derived DAMPs might allow us to develop new therapeutic approaches for hemolytic diseases.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Ferryl hemoglobin Heme Hemolysis IL-1β Macrophage NLRP3 inflammasome activation
Megjelenés:	Biochimica et biophysica acta. Molecular basis of disease. - 1865 : 2 (2019), p. 464-475. -
További szerzők:	Tóth Andrea (1992-) (molekuláris biológus) Balogh Enikő (1987-) (molekuláris biológus) Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos) Erdei Judit Zsuzsa (1992-) (vegyész) Ryffel, Bernhard Paragh György (1953-) (belgyógyász) Cordero, Mario D. Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:	NKFIH K116024 NKFIH GINOP-2.3.2-15-2016-00005 GINOP
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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