Activation of the STAT1 signalling pathway in lupus nephritis in MRL/lpr mice.
Interferons (IFNs), type I (alpha/beta) and type II (gamma), comprise a family of multifunctional cytokines with antiviral, antiproliferative and immunomodulating properties. Both type I and type II IFNs have been heavily implicated in the pathogenesis of systemic lupus erythematosus (SLE). The biological effects of IFNs are mediated through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in which both IFN-alpha/beta and IFN-gamma activate the transcription factor STAT1. However, little is known about the pathogenic significance of STAT1 in SLE. At this point, we examined the expression and activation of STAT1 in the kidney of MRL/lpr mice with lupus nephritis (LN) by immunohistochemistry, Western botting and real time quantitative RT-PCR. Increased levels of total STAT1 protein and its activated/phosphorylated form were detected in kidney samples from MRL/lpr mice with LN as compared to those from control mice. Phosphorylated STAT1 was predominantly detected in glomeruli cells. Gene expression of the STAT induced feedback inhibitors suppressor of cytokine signalling-1 (SOCS-1) and SOCS-3 was also enhanced in MRL/lpr mice. In MRL/lpr mesangial cells, both IFN-alpha and IFN-gamma rapidly induced the phosphorylation of STAT in vitro. Our results demonstrate that expression and activation of STAT1 are significantly increased in murine lupus nephritis, and indicate that STAT1 signalling pathway may play an important role in the pathogenesis of kidney inflammation.
Dong
J
J
Department of Rheumatology, Shandong Provincial Hospital, Shandong University, Jinan, China. dongjing2188@yahoo.com
Wang
Q X
QX
Zhou
C Y
CY
Ma
X F
XF
Zhang
Y C
YC
D000818:Animals; D005260:Female; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D050794:STAT1 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction
D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse