Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Biochem Biophys Res Commun. 2014 Jan 31;444(1):75-80. doi: 10.1016/j.bbrc.2014.01.015. Epub 2014 Jan 14.
Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.
坏死腺泡细胞引发的炎症反应导致了急性胰腺炎（AP）的病理生理学变化，但具体机制尚不清楚。最近的研究表明，坏死细胞释放的亲环蛋白 A（CypA）参与了几种炎症性疾病的发病机制。因此，我们研究了亲环蛋白 A（CypA）在牛磺胆酸钠（STC）诱导的实验性急性胰腺炎中的作用。CypA 在破坏的腺泡细胞、浸润的炎症细胞和管状复合物中明显上调和广泛表达。在体外，CypA 由胆囊收缩素（CCK）诱导从受损的腺泡细胞中释放。rCypA（重组 CypA）加重了 CCK 诱导的腺泡细胞坏死，促进了核因子（NF）-κB p65 的激活，并增加了细胞因子的产生。总之，CypA 通过 NF-κB 通路上调腺泡细胞炎症细胞因子的表达，促进胰腺损伤。
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