@article{10.1172/jci.insight.141420, author = {Kyle L. Poulsen AND Xiude Fan AND Christopher D. Kibler AND Emily Huang AND Xiaoqin Wu AND Megan R. McMullen AND Lin Leng AND Richard Bucala AND Meritxell Ventura-Cots AND Josepmaria Argemi AND Ramon Bataller AND Laura E. Nagy}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Role of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis}, year = {2021}, month = {6}, volume = {6}, url = {https://insight.jci.org/articles/view/141420}, abstract = {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 (MifΔHep) 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.}, number = {11}, doi = {10.1172/jci.insight.141420}, url = {https://doi.org/10.1172/jci.insight.141420}, }