Full metadata record
DC Field | Value | Language |
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dc.creator | Labiano, I. (Ibone) | - |
dc.creator | Agirre-Lizaso, A. (Aloña) | - |
dc.creator | Olaizola, P. (Paula) | - |
dc.creator | Echebarria, A. (Anne) | - |
dc.creator | Huici-Izagirre, M. (Maider) | - |
dc.creator | Olaizola, I. (Irene) | - |
dc.creator | Esparza-Baquer, A. (Aitor) | - |
dc.creator | Sharif, O. (Omar) | - |
dc.creator | Hijona, E. (Elizabeth) | - |
dc.creator | Milkiewicz, P. (Piotr) | - |
dc.creator | Milkiewicz, P. (Piotr) | - |
dc.creator | González-Romero, F. (Francisco) | - |
dc.creator | Aspichueta, P. (Patricia) | - |
dc.creator | Monte, M.J. (María J.) | - |
dc.creator | Marin, J.J.G (Jose J.G.) | - |
dc.creator | Vucur, M. (Mihael) | - |
dc.creator | Luedde, T. (Tom) | - |
dc.creator | Marzioni, M. (Marco) | - |
dc.creator | Mann, D.A. (Derek A.) | - |
dc.creator | Bujanda, L. (Luis) | - |
dc.creator | Rodrigues, P.M. (Pedro M.) | - |
dc.creator | Bañales-Asurmendi, J.M. (Jesus Maria) | - |
dc.creator | Perugorria, M.J. (María J.) | - |
dc.date.accessioned | 2023-04-19T11:34:12Z | - |
dc.date.available | 2023-04-19T11:34:12Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Labiano, I. (Ibone); Agirre-Lizaso, A. (Aloña); Olaizola, P. (Paula); et al. "TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation". Journal Of Hepatolgy (Online). 77 (4), 2022, 991 - 1004 | es |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | https://hdl.handle.net/10171/66021 | - |
dc.description.abstract | Background & Aims: Inflammation, particularly that mediated by bacterial components translocating from the gut to the liver and binding to toll-like receptors (TLRs), is central to cholestatic liver injury. The triggering receptor expressed on myeloid cells-2 (TREM-2) inhibits TLR-mediated signaling and exerts a protective role in hepatocellular injury and carcinogenesis. This study aims to evaluate the role of TREM-2 in cholestasis.Methods: TREM-2 expression was analyzed in the livers of pa-tients with primary biliary cholangitis (PBC) or primary scle-rosing cholangitis (PSC), and in mouse models of cholestasis. Wild-type (WT) and Trem-2 deficient (Trem-2-/-) mice were subjected to experimental cholestasis and gut sterilization. Pri-mary cultured Kupffer cells were incubated with lipopolysac-charide and/or ursodeoxycholic acid (UDCA) and inflammatory responses were analyzed.Results: TREM-2 expression was upregulated in the livers of patients with PBC or PSC, and in murine models of cholestasis. Compared to WT, the response to bile duct ligation (BDL)-induced obstructive cholestasis or alpha-naphtylisothiocyanate (ANIT)-induced cholestasis was exacerbated in Trem-2-/-mice. This was characterized by enhanced necroptotic cell death, in-flammatory responses and biliary expansion. Antibiotic treat-ment partially abrogated the effects observed in Trem-2-/-mice after BDL. Experimental overexpression of TREM-2 in the liver of WT mice downregulated ANIT-induced IL-33 expression and neutrophil recruitment. UDCA regulated Trem-1 and Trem-2 expression in primary cultured mouse Kupffer cells and damp-ened inflammatory gene transcription via a TREM-2-dependent mechanism.Conclusions: TREM-2 acts as a negative regulator of inflamma-tion during cholestasis, representing a novel potential thera-peutic target.Lay summary: Cholestasis (the reduction or cessation of bile flow) causes liver injury. This injury is exacerbated when gut-derived bacterial components interact with receptors (spe-cifically Toll-like receptors or TLRs) on liver-resident immune cells, promoting inflammation. Herein, we show that the anti-inflammatory receptor TREM-2 dampens TLR-mediated signaling and hence protects against cholestasis-induced liver injury. Thus, TREM-2 could be a potential therapeutic target in cholestasis. | - |
dc.language.iso | en | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.subject | Área de Medicina Clínica y Epidemiología | - |
dc.subject | Single-cell RNA-seq | - |
dc.subject | Naive state | - |
dc.subject | Trophectoderm | - |
dc.subject | 8CLCs | - |
dc.title | TREM-2 Plays a Protective Role in Cholestasis By Acting as a Negative Regulator of Inflammation | - |
dc.type | info:eu-repo/semantics/article | - |
dc.relation.publisherversion | https://pubmed.ncbi.nlm.nih.gov/35750136/ | - |
dc.description.note | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) | - |
dc.identifier.doi | 10.1016/j.jhep.2022.05.044 | - |
dadun.citation.endingPage | 1004 | - |
dadun.citation.number | 4 | - |
dadun.citation.publicationName | JOURNAL OF HEPATOLOGY (ONLINE) | - |
dadun.citation.startingPage | 991 | - |
dadun.citation.volume | 77 | - |
dc.identifier.pmid | 35750136 | - |
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