Interleukin-1 participates in the progression from liver injury to fibrosis

Gieling, Roben, Wallace, Karen and Han, Yuan-Ping (2009) Interleukin-1 participates in the progression from liver injury to fibrosis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 296 (6). G1324-G1331. ISSN 0193-1857

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Abstract

Interleukin-1 (IL-1) is rapidly expressed in response to tissue damage; however, its role in coordinating the progression from injury to fibrogenesis is not fully understood. Liver fibrosis is a consequence of the activation of hepatic stellate cells (HSCs), which reside within the extracellular matrix (ECM) of subsinusoids. We have hypothesized that, among the hepatic inflammatory cytokines, IL-1 may directly activate HSCs through autocrine signaling and stimulate the matrix metalloproteinases (MMPs) produced by HSCs within the space of Disse, resulting in liver fibrogenesis. In this study, we first established a temporal relationship between IL-1, MMPs, HSC activation, and early fibrosis. The roles of IL-1 and MMP-9 in HSC activation and fibrogenesis were determined by mice deficient of these genes. After liver injury, IL-1, MMP-9, and MMP-13 levels were found to be elevated before the onset of HSC activation and fibrogenesis. IL-1 receptor-deficient mice exhibited ameliorated liver damage and reduced fibrogenesis. Similarly, advanced fibrosis, as determined by type-I and -III collagen mRNA expression and fibrotic septa, was partially attenuated by the deficiency of IL-1. In the early phase of liver injury, the MMP-9, MMP-13, and TIMP-1 expression correlated well with IL-1 levels. In injured livers, MMP-9 was predominantly colocalized to desmin-positive cells, suggesting that HSCs are MMP-producing cells in vivo. MMP-9-deficient mice were partially protected from liver injury and HSC activation. Thus IL-1 is an important participant, along with other cytokines, and controls the progression from liver injury to fibrogenesis through activation of HSCs in vivo.

Item Type:	Article
Uncontrolled Keywords:	hepatic stellate cell, matrix metalloproteinase, carbon tetrachloride, thioacetamide, bile duct ligation
Subjects:	B100 Anatomy, Physiology and Pathology
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Becky Skoyles
Date Deposited:	12 Jul 2018 10:25
Last Modified:	11 Oct 2019 20:00
URI:	http://nrl.northumbria.ac.uk/id/eprint/34956

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