Hepatic serum amyloid A1 aggravates T cell-mediated hepatitis by inducing chemokines via toll-like receptor 2 in mice

Young Rae Ji, Hei Jung Kim, Ki Beom Bae, Sanggyu Lee, Myoung Ok Kim, Zae Young Ryoo

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Serum amyloid A is a proinflammatory molecule that induces leukocyte infiltration and promotes neutrophil adhesion to endothelial cells under inflammatory conditions. The aim of this study was to examine whether Saa1 aggravates T cell-mediated hepatitis by inducing chemokines in a liver-specific, Saa1-overexpressing, transgenic (TG) mouse model. We generated TG mice in which Saa1 was overexpressed specifically in liver tissue. The chemokines monocyte chemotactic protein 1 (MCP1), MIP1α, MIP1β, interferon σ-induced protein 10 (IP-10), and eotaxin were induced in Saa1 TG mice. After concanavalin A treatment, Saa1 expression was higher in Saa1 TG mice than in WT mice. More severe liver injury, increased hepatocyte apoptosis, and higher levels of hepatic enzymes were observed in Saa1 TG mice than inWT mice. Liver infiltration of CD4+ T cells and macrophages increased after inducing hepatitis. Activation of T cells was higher in Saa1 TG mice than inWT mice, and the populations of Th17 cells and regulatory T cells were altered by overexpressing Saa1 in TG mice. Secretion of various cytokines, such as interferon σ, tumor necrosis factorα, and interleukin 6, increased in Saa1 TG mice. Injecting a Toll-like receptor 2 (TLR2) antagonist in vivo inhibited chemokine expression and IκBα phosphorylation and showed that the induction of chemokines by Saa1 was dependent on TLR2. Hepatic Saa1 accelerated T cell-mediated hepatitis by inducing chemokine production and activating T cells by TLR2. Therefore, Saa1 might be a novel inflammatory factor that acts as a chemokine modulator in hepatitis.

Original languageEnglish (US)
Pages (from-to)12804-12811
Number of pages8
JournalJournal of Biological Chemistry
Volume290
Issue number20
DOIs
StatePublished - May 15 2015

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