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


CONCLUSIONS
These results demonstrate that mesalamine enhances B7-H1 expression on HSCs, and thus, induces T-cell apoptosis and attenuates autoimmune liver injury.
Departments of Internal Medicine and Liver Research Institute Pathology, Seoul National University College of Medicine Department of Internal Medicine and Healthcare Research Institute, Korea.
Jeong-Hoon
JH
Lee
Jung-Hwan
JH
Yoon
Yu-Jeong
YJ
Lee
Jong In
JI
Yang
Min-Sun
MS
Kwak
Eun Ju
EJ
Cho
Eun Sun
ES
Jang
Su Jong
SJ
Yu
Dae Hee
DH
Choi
Eun Uk
EU
Jung
Hwi Young
HY
Kim
Bo Hyun
BH
Kim
Goh Eun
GE
Chung
Yoon Jun
YJ
Kim
Ja-June
JJ
Jang
Chung Yong
CY
Kim
Hyo-Suk
HS
Lee