Mesalamine-induced B7-H1 expression on hepatic stellate cells attenuates autoimmune liver injury

Jeong Hoon Lee, Jung Hwan Yoon, Yu Jeong Lee, Jong In Yang, Min Sun Kwak, Eun Ju Cho, Eun Sun Jang, Su Jong Yu, Dae Hee Choi, Eun Uk Jung, Hwi Young Kim, Bo Hyun Kim, Goh Eun Chung, Yoon Jun Kim, Ja June Jang, Chung Yong Kim, Hyo Suk Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Aim: Hepatic stellate cells (HSCs) have immune regulatory functions. Mesalamine is an effective immune regulatory drug for inflammatory bowel disease. Thus, we hypothesized that mesalamine may also modulate the immune regulatory functions of HSCs. Since B7-H1 plays a crucial role in regulating T-cell apoptosis, we evaluated if mesalamine induces B7-H1 expression on HSCs, and if so, whether mesalamine attenuates autoimmune liver injury in vivo.Methods: LX-2 cells, an immortalized human HSC cell line, and human peripheral T-cells were used in this study. B7-H1 expression on LX-2 cells following mesalamine treatment was examined by using flow cytometry. Cell viability was analyzed by MTS assay. Concanavalin-A (ConA) mice hepatitis model was used for in vivo study.Results: Flow cytometry showed that mesalamine treatment increased the B7-H1-expressing LX-2 cell fraction from 45.4% to 88.2%, of which increment is equivalent to that of positive control (29.9%, interferon γ-treated cells). Human T-cells incubated with LX-2 cells showed significantly less cell viability in the presence of mesalamine than cells without mesalamine treatment (P < 0.001). Histological examination revealed that hepatic necroinflammation was significantly attenuated by mesalamine pretreatment (P = 0.019), although serum levels of aminotransferases were not significantly reduced. During the 24-h period following ConA injection, 1 of 10 mice pretreated with mesalamine and 3 of 10 mice without pretreatment died.Conclusion: These results demonstrate that mesalamine enhances B7-H1 expression on HSCs, and thus, induces T-cell apoptosis and attenuates autoimmune liver injury.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalHepatology Research
Volume41
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Apoptosis
  • Autoimmune hepatitis
  • B7-H1
  • Concanavalin A
  • Mesalamine

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