ABSTRACT
Objective To explore the activation and function of Janus protein-tyrosine kinase (JAK)/ signal transducer and activator of transcription (STAT1) signal transduction pathway in kidney,lung and brain of MRL/lpr mice.Methods MRL/lpr mice with systemic lupus erythematosus (SLE) were studied at the age of 12 weeks up.Non-SLE MRL/lpr mice were used as controls.We used phosphospecific antibodies to detect STAT1 activation in kidney,lung and brain by immunohistochemistry and Western blots.Gene expression of the STAT induced feedback inhibitors of cytokine signaling 1 (SOCS-1) was investigated by SYBR green I real-time reverse transcriptase polymerase chain reaction (PCR).Results Phosphorylation of STAT1 protein was markedly activated in these three organs,although renal and pulmonary STAT1 activation were much more evidently activated.SOCS-1 gene expression increased in all three organs,while renal SOCS-1 gene expres- sion increased less than lung and brain.Conclusion The activation of JAK/STATI signal transduction path- way may be pathogenic in the organ involvement and progression of SLE.The pathogenesis of lupus nephritis may also be associated with the down-regulation of SOCS-1 feedback inhibition.
ABSTRACT
Objective To explore the association between ankylosing spondylitis(AS)with the poly- morphism in -308 site of tumor necrosis factor(TNF)-?promoter region. Methods The literature about AS and polymorphism in -308 site of TNF-?promoter region were searched and the meta analysis as performed. Results Eight studies enrolled 987 AS patients and 922 controls in total. The analysis showed that the fre- quencies of alleles and the genotypes had no statistical difference between AS group and the control group [OR=0.86(0.53, 1.38), P=0.53; OR=0.90(0.52, 1.55), P=0.69]. But the frequencies of alleles of western origin had statistical difference between AS group and the control group [OR=0.75(0.59, 0.96), P=0.02]; The TNF-?gene promoter polymorphism may play a role in the severity of sacroiliitis[OR=0.37(0.15. 0.90), P=0.03]. Conclusion The meta-analysis reveales that the alleles of -308 site of TNF-?promoter region may be associated with AS in western ethnical group and play a role in the severity of saeroiliitis.