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IL-8 signaling is up-regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present.
- Source :
-
Experimental and molecular pathology [Exp Mol Pathol] 2015 Oct; Vol. 99 (2), pp. 320-5. Date of Electronic Publication: 2015 Aug 08. - Publication Year :
- 2015
-
Abstract
- Chemokines and their receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. The chemokine CXCL8, also known as interleukin-8 (IL-8), is a proinflammatory molecule that has functions within the tumor microenvironment. Deregulation of IL-8 signaling is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of IL-8 signaling by RNA sequencing (RNA-Seq) analyses. Real-time PCR analysis of CXCR2 further shows a 6-fold up-regulation in AH livers and a 26-fold up-regulation in the livers of DDC re-fed mice. IL-8 mRNA was also significantly up-regulated in AH livers and DDC re-fed mice livers. This indicates that CXCR2 and IL-8 may be crucial for liver MDB formation. MDB containing balloon hepatocytes in AH livers had increased intensity of staining of the cytoplasm for both CXCR2 and IL-8. Overexpression of IL-8 leads to an increase of the mitogen activated protein kinase (MAPK) cascade and exacerbates the inflammatory cycle. These observations constitute a demonstration of the altered regulation of IL-8 signaling in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by IL-8 signaling in AH.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biomarkers metabolism
Blotting, Western
Cells, Cultured
Gene Expression Profiling
Hepatitis, Alcoholic etiology
Hepatitis, Alcoholic pathology
Hepatocytes cytology
High-Throughput Nucleotide Sequencing
Humans
Immunoenzyme Techniques
Interleukin-8 genetics
Liver cytology
Male
Mallory Bodies pathology
Mice
Mice, Inbred C3H
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Hepatitis, Alcoholic metabolism
Hepatocytes metabolism
Interleukin-8 metabolism
Liver metabolism
Mallory Bodies metabolism
Pyridines toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0945
- Volume :
- 99
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental and molecular pathology
- Publication Type :
- Academic Journal
- Accession number :
- 26260904
- Full Text :
- https://doi.org/10.1016/j.yexmp.2015.08.002