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Role of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis

The chemokine system of ligands and receptors is implicated in the progression of alcohol-associated hepatitis (AH). Finding upstream regulators could lead to novel therapies. This study involved coordinated expression of chemokines in livers of healthy controls (HC) and patients with AH in 2 distin...

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Detalles Bibliográficos
Autores principales: Poulsen, Kyle L., Fan, Xiude, Kibler, Christopher D., Huang, Emily, Wu, Xiaoqin, McMullen, Megan R., Leng, Lin, Bucala, Richard, Ventura-Cots, Meritxell, Argemi, Josepmaria, Bataller, Ramon, Nagy, Laura E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262327/
https://www.ncbi.nlm.nih.gov/pubmed/33945507
http://dx.doi.org/10.1172/jci.insight.141420
Descripción
Sumario:The chemokine system of ligands and receptors is implicated in the progression of alcohol-associated hepatitis (AH). Finding upstream regulators could lead to novel therapies. This study involved coordinated expression of chemokines in livers of healthy controls (HC) and patients with AH in 2 distinct cohorts of patients with various chronic liver diseases. Studies in cultured hepatocytes and in tissue-specific KO were used for mechanistic insight into a potential upstream regulator of chemokine expression in AH. Selected C-X-C chemokine members of the IL-8 chemokine family and C-C chemokine CCL20 were highly associated with AH compared with HC but not in patients with liver diseases of other etiologies (nonalcoholic fatty liver disease [NAFLD] and hepatitis C virus [HCV]). Our previous studies implicate macrophage migration inhibitory factor (MIF) as a pleiotropic cytokine/chemokine with the potential to coordinately regulate chemokine expression in AH. LPS-stimulated expression of multiple chemokines in cultured hepatocytes was dependent on MIF. Gao-binge ethanol feeding to mice induced a similar coordinated chemokine expression in livers of WT mice; this was prevented in hepatocyte-specific Mif–KO (Mif(ΔHep)) mice. This study demonstrates that patients with AH exhibit a specific, coordinately expressed chemokine signature and that hepatocyte-derived MIF might drive this inflammatory response.