Mallory Denk Body Formation in Alcoholic Hepatitis: The Pivotal Role of Interleukin-8 Signaling

Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding diethyl 1,4-dehydro-2,4,6-trimethyl-3,5-pyridine-dicarboxylate (DDC). The chemokine CXCL8, also known as interleukin-8 (IL-8) and its receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. We reported previously the marked upregulation of IL-8 signaling in AH and DDC fed mice with MDBs present by RNA sequencing (RNA-Seq) analyses. Central molecules including IL-8 and the chemokine (C-X-C motif) receptor 2 (CXCR2) of this pathway were significantly upregulated in the livers of DDC refed mice and human liver biopsies from AH livers. MDB containing balloon hepatocytes in AH livers have increased intensity of staining of the cytoplasm for both IL-8 and CXCR2. Taken conjointly, these data indicates a crucial role of IL-8 signaling during MDB formation, and IL-8 and CXCR2 may be targeted as biomarkers for personalized treatment of AH.