吡格列酮，一种过氧化物酶体增殖物激活受体γ（PPARγ）配体，通过抑制雨蛙肽处理的AR42J细胞中IκB激酶的激活来抑制核因子κB（NFκB）的激活。
Pioglitazone, a PPARgamma ligand, suppresses NFkappaB activation through inhibition of IkappaB kinase activation in cerulein-treated AR42J cells.
作者信息
Wan Hongyu, Yuan Yaozong, Qian Aihua, Sun Yan, Qiao Minmin
机构信息
Department of Gastroenterology, Affiliated Ruijin Hospital of Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai 200025, China.
出版信息
Biomed Pharmacother. 2008 Sep;62(7):466-72. doi: 10.1016/j.biopha.2007.10.012. Epub 2007 Dec 17.
BACKGROUND AND AIM
NFkappaB plays a major role in the immune and inflammation responses of pancreatitis. Recently, there is increasing evidence that the expression and activity of PPARgamma may participate in the activity of NFkappaB. Therefore, we investigated a putative relationship of the two transcription factors in cerulein-treated pancreatic acinar AR42J cells.
METHOD
AR42J were stimulated by cerulein with or without the presence of a PPARgamma activator pioglitazone or a PPARgamma antagonist GW9662.
RESULTS
Treatment of AR42J cells with pioglitazone attenuated cerulein induced p50 and p65 NFkappaB dimer activity in the nucleus as measured by transcription factor assay. Cytosolic expression of IkappaBalpha protein was reduced by cerulein, basal signalling was not influenced by the PPARgamma inhibitor GW9662 and pioglitazone. Adversely, the inhibitory effect of pioglitazone on NFkappaB activity induced by cerulein was almost reversed by GW9662.
CONCLUSION
These findings provide evidence for the involvement of the nuclear hormone receptors PPARgamma in the activity of NFkappaB in cerulein-treated AR42J cells.
背景与目的
核因子κB（NFκB）在胰腺炎的免疫和炎症反应中起主要作用。最近，越来越多的证据表明过氧化物酶体增殖物激活受体γ（PPARγ）的表达和活性可能参与NFκB的活性。因此，我们研究了在雨蛙肽处理的胰腺腺泡AR42J细胞中这两种转录因子之间的假定关系。
方法
在有或无PPARγ激活剂吡格列酮或PPARγ拮抗剂GW9662存在的情况下，用雨蛙肽刺激AR42J细胞。
结果
通过转录因子分析测定，用吡格列酮处理AR42J细胞可减弱雨蛙肽诱导的细胞核中p50和p65 NFκB二聚体活性。雨蛙肽可降低IκBα蛋白的胞质表达，基础信号传导不受PPARγ抑制剂GW9662和吡格列酮的影响。相反，GW9662几乎逆转了吡格列酮对雨蛙肽诱导的NFκB活性的抑制作用。
结论
这些发现为核激素受体PPARγ参与雨蛙肽处理的AR42J细胞中NFκB的活性提供了证据。
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