Kato A, Yoshidome H, Edwards M J, Lentsch A B
Department of Surgery, University of Louisville School of Medicine, J. G. Brown Cancer Center, Kentucky 40202, USA.
Inflamm Res. 2000 Jun;49(6):275-9. doi: 10.1007/PL00000207.
The ability of interleukin-4 (IL-4) to modulate activation of the transcription factors, NF-kappaB and STAT6, reduce proinflammatory cytokine expression and protect against liver injury induced by ischemia/reperfusion was assessed.
C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by 1 or 8 h of reperfusion with or without intravenous administration of 1 microg (0.5 microg just prior to ischemia, 0.5 microg at reperfusion) recombinant murine IL-4. Liver expression of TNFalpha mRNA was determined by RT-PCR. Activation of NF-kappaB and STAT6 in liver nuclear extracts was assessed by mobility shift assay.
Hepatic ischemia/reperfusion increased hepatic expression of tumor necrosis factor-alpha (TNFalpha), induced significant neutrophil accumulation and liver injury. Treatment with IL-4 greatly suppressed liver TNFalpha mRNA expression, neutrophil accumulation and liver injury. IL-4 had no effect on liver NF-kappaB activation, but greatly increased the activation of STAT6.
The data suggest that STAT6 activation by IL-4 may be responsible for the protective effects of this cytokine.
评估白细胞介素-4（IL-4）调节转录因子NF-κB和STAT6的激活、降低促炎细胞因子表达以及预防缺血/再灌注诱导的肝损伤的能力。
C57BL/6小鼠经历90分钟部分肝缺血，随后进行1或8小时再灌注，同时静脉注射1微克（缺血前0.5微克，再灌注时0.5微克）重组鼠IL-4或不注射。通过RT-PCR测定肝脏肿瘤坏死因子α（TNFα）mRNA的表达。通过迁移率变动分析评估肝细胞核提取物中NF-κB和STAT6的激活情况。
肝缺血/再灌注增加了肝脏肿瘤坏死因子-α（TNFα）的表达，诱导了显著的中性粒细胞聚集和肝损伤。IL-4治疗极大地抑制了肝脏TNFα mRNA表达、中性粒细胞聚集和肝损伤。IL-4对肝脏NF-κB激活没有影响，但极大地增加了STAT6的激活。
数据表明IL-4激活STAT6可能是该细胞因子发挥保护作用的原因。
