상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Small heterodimer partner deficiency increases inflammatory liver injury through C-X-C motif chemokine ligand 2-driven neutrophil recruitment in mice

Authors 

Jung-Ran NohYong-Hoon KimD K KimJung Hwan HwangKyoung Shim KimDong-Hee ChoiSeon-Jin LeeHee Gu LeeT G LeeH L WengS DooleyH S ChoiChul Ho Lee

Publisher 

Oxford University Press (OUP)

Issue Date 

2018

Citation 

Toxicological Sciences

Keywords 

ChemokineInflammationLiver injurySmall heterodimer partner

Abstract 

Although detailed pathophysiological mechanisms of fulminant hepatitis remain elusive, immune cell recruitment with excessive cytokine production is a well-recognized hallmark of the disease.We determined the function of orphan nuclear receptor small heterodimer partner (SHP) in concanavalin A (ConA)-induced hepatitis model. Male C57BL/6 J mice were injected intravenously with either a lethal dose (25 mg/kg) or a sub-lethal dose (15 mg/kg) of ConA. For the C-X-C motif chemokine ligand (CXCL) 2 neutralization study,mice were intravenously administered anti-mouse CXCL2 antibody (100 lg/mouse). Thirtysix hours following lethal dose of ConA administration, 47% wild type (WT)mice were alive, whereas > 85% of Shp knockout (KO) were dead. Shp KO mice were highly susceptible to ConA-induced liver injury and exhibited increased liver necrosis upon sublethal dose of ConA administration. FACS analysis and immunohistochemical staining showed significantly higher neutrophil infiltration in Shp KO mice, as compared withWTmice. We found that also in theWT situation, Shp expression gradually decreased, while Cxcl2 expression increased until 6 h, and vice versa at 24 h upon ConA-treatment, indicating an inverse correlation between Shp and Cxcl2 expression during ConA-induced hepatitis. Furthermore, in vivo neutralization of CXCL2 with neutralizing antibody reduces ConA-induced plasma ALT and AST levels, hepatocyte death and neutrophil infiltration in Shp KO mice. Collectively, these results confirm that lacking of SHP results in CXCL2-dependent neutrophil infiltration in ConA-induced liver damage. SHP plays a protective, anti-inflammatory role in liver during acute liver inflammation

ISSN 

1096-6080

Link 

http://dx.doi.org/10.1093/toxsci/kfy030

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)