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Nuclear expression of interleukin-33 in pancreatic stellate cells.

机译:白细胞介素33在胰腺星状细胞中的核表达。

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摘要

Activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have suggested a role of IL-33, a newly identified IL-1 family member, in fibrosis. We here examined the expression of IL-33 and the IL-33-mediated regulation of cell functions in PSCs. PSCs were isolated from human and rat pancreas tissues. The expression of IL-33 was examined by Western blotting, PCR, ELISA, and immunostaining. The roles of IL-33 in the regulation of PSC functions were examined by using recombinant IL-33 and small interfering RNA. Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1beta, TNF-alpha, PDGF-BB, and IFN-gamma, but not TGF-beta1. Nuclear IL-33 expression was also observed in the pancreatic acinar and ductal cells. IL-1beta induced IL-33 expression mainly through the activation of NF-kappaB and ERK pathways and partially through that of p38 MAP kinase, whereas PDGF-BB induced IL-33 expression mainly through the activation of ERK pathway. PSCs expressed soluble ST2, ST2L, and IL-1RAcP, but the expression level of ST2L was relatively low. Recombinant IL-33 did not stimulate key cell functions of PSCs. Decreased IL-33 expression by small interfering RNA resulted in decreased proliferation in response to PDGF-BB. In conclusion, activated PSCs expressed IL-33 in the nucleus. IL-33 might regulate the PDGF-induced proliferation in PSCs.
机译:活化的胰腺星状细胞(PSC)在慢性胰腺炎和胰腺癌的胰腺纤维化中起关键作用。最近的研究表明,新发现的IL-1家族成员IL-33在纤维化中的作用。我们在这里检查了PSC中IL-33的表达和IL-33介导的细胞功能调节。从人和大鼠胰腺组织中分离出PSC。通过Western印迹,PCR,ELISA和免疫染色检查IL-33的表达。通过使用重组IL-33和小的干扰RNA,检查了IL-33在PSC功能调节中的作用。活化的PSC在细胞核中表达IL-33,而IL-1beta,TNF-alpha,PDGF-BB和IFN-γ却增加了表达,但TGF-beta1却没有。在胰腺腺泡和导管细胞中也观察到了核IL-33表达。 IL-1beta主要通过激活NF-kappaB和ERK途径诱导IL-33表达,部分通过p38 MAP激酶诱导,而PDGF-BB主要通过激活ERK途径诱导IL-33表达。 PSC表达可溶性ST2,ST2L和IL-1RAcP,但是ST2L的表达水平相对较低。重组IL-33不会刺激PSC的关键细胞功能。小分子干扰RNA降低IL-33表达会导致对PDGF-BB的增殖减少。总之,活化的PSC在细胞核中表达IL-33。 IL-33可能调节PDGF诱导的PSC增殖。

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