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001-es BibID:	BIBFORM103624
035-os BibID:	(WoS)000923633900005 (Scopus)85142716887
Első szerző:	Cho, Yeonhee
Cím:	Neutrophil extracellular traps contribute to liver damage and increase defective low-density neutrophils in alcoholic hepatitis / Cho Yeonhee, Bukong Terence Ndonyi, Tornai David, Babuta Mrigya, Vlachos Ioannis S., Kanata Eleni, Catalano Donna, Szabo Gyongyi
Dátum:	2023
ISSN:	0168-8278
Megjegyzések:	Background & Aims In alcoholic hepatitis (AH), inflammation and neutrophil counts correlate with poor clinical outcomes. Here, we investigated how neutrophils contribute to liver damage in AH. Methods We isolated blood neutrophils from AH patients to examine neutrophils extracellular traps (NETs) and performed RNA sequencing to explore unique characteristics. Results We found a significant increase of NET production in AH. We also observed a unique low-density neutrophil (LDNs) population in AH patients and alcohol-fed mice that was not present in healthy controls. Transcriptome analysis of peripheral LDNs and high-density neutrophils (HDNs) from AH patients revealed that LDNs exhibit a functionally exhausted phenotype, while HDNs are activated. Indeed, we found that AH HDNs have increased resting reactive oxygen species (ROS) and produce higher ROS upon LPS stimulation than control HDNs, whereas AH LDNs fail to respond to LPS. We show that LDNs are generated from HDNs after alcohol-induced NET release in vitro, and this LDN subset has decreased functionality including reduced phagocytosis. Moreover, LDNs showed reduced homing capacity and clearance by macrophage efferocytosis; therefore, dysfunctional neutrophils could remain in the circulation and liver. Depletion of both HDNs and LDNs in vivo prevented alcohol-induced NET production and liver damage in mice. Granulocyte-colony stimulating factor (G-CSF) treatment also ameliorated alcohol-induced liver injury in mice. Conclusion Neutrophils contribute to liver damage through increased NET formation which increases defective LDNs in AH. Alcohol induces neutrophil phenotype changes; HDNs are activated whereas LDNs are defective. Our findings provide mechanistic insights for therapeutic interventions in AH.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal Of Hepatology. - 78 : 1 (2023), p. 28-44. -
További szerzők:	Bukong, Terence Ndonyi Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Babuta, Mrigya Vlachos, Ioannis S. Kanata, Eleni Catalano, Donna Szabó Gyöngyi
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM082950
Első szerző:	Lowe, Patrick
Cím:	Inhibition of the Inflammasome Signaling Cascade Reduces Alcohol Consumption in Female But Not Male Mice / Patrick P. Lowe, Yeonhee Cho, David Tornai, Sahin Coban, Donna Catalano, Gyongyi Szabo
Dátum:	2020
ISSN:	0145-6008 1530-0277
Megjegyzések:	BACKGROUND: Alcohol use disorder is a significant societal and medical burden that is associated with both organ pathology and addiction. Excessive alcohol use results in neuroinflammation characterized by activation of the inflammasome, a multiprotein complex, and IL-1? increase in the brain. Recent studies suggest that inflammation could contribute to alcohol addiction. Here, we targeted components of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome cascade, which senses and responds to immunologic stimuli, to determine whether NLRP3 inhibition modulates alcohol consumption. METHODS: C57BL/6J male and female mice were provided a 2-bottle choice of alcohol at increasing concentrations (3, 6, 9, and 12%, 4 days each) or water, and some were treated with daily injections of an NLRP3 inhibitor (MCC950), a caspase-1 inhibitor (VX765), IL-1 receptor antagonist (IL-1ra; anakinra), or vehicle injection. RESULTS: Treatment with VX765, MCC950, and IL-1ra significantly reduced alcohol consumption and preference in female mice (p < 0.05). Treatment with MCC950 and IL-1ra reduced alcohol consumption, while IL-1ra reduced alcohol preference in male mice (p < 0.05). VX765 did not affect alcohol consumption or preference in male mice. CONCLUSIONS: These findings highlight gender differences in alcohol preference and demonstrate that inhibition of different steps in inflammasome signaling can reduce alcohol consumption in females. Inhibition of NLRP3 inflammasome activation and the inflammasome-IL-1? cascade opens novel insights into the development of new therapies to address alcohol use disorder in an era of targeted and precision medicine.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Alcohol Anakinra NLRP3 Caspase-1 Interleukin-1 Beta
Megjelenés:	Alcoholism, Clinical and Experimental Research. - 44 : 2 (2020), p. 567-578. -
További szerzők:	Cho, Yeonhee Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Coban, Sahin Catalano, Donna Szabó Gyöngyi
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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