title: siRNA-based targeting of fractalkine overexpression suppresses inflammation             development in a severe acute pancreatitis rat model.
abstract: Fractalkine (FKN), a chemokine that acts as both an adhesion molecule and a chemoattractant, is expressed in many inflammatory diseases. Chemokines play a crucial role in severe acute pancreatitis (SAP). This study used adenovirus-mediated siRNA to target FKN overexpression and assessed its ability to suppress inflammation development in a SAP rat model. Adenovirus-mediated FKN siRNA was transfected into cerulein-stimulated AR42J cells. The growth of cerulein-stimulated AR42J cells was determined by colony formation and MTT assays. The inhibitory effect of the FKN siRNA was studied in a SAP rat model in vivo and detected by ELISA, RT-PCR, western blot analysis and immunohistochemistry. FKN, IL-8 and TNF-α were found to be overexpressed in cerulein-stimulated AR42J cells by ELISA and western blot analysis (P<0.05). The animal experiments confirmed that FKN siRNA could inhibit inflammation development in SAP. The values of serum FKN, TNF-α and IL-8 levels were decreased after FKN siRNA treatment (P<0.05). Furthermore, western blotting and RT-PCR analysis showed that FKN protein and mRNA levels were decreased after injection with FKN siRNA (P<0.05). Immunohistochemistry also showed that inflammation was decreased after injection with FKN-siRNA in the SAP rat model. Treatment with siRNA can inhibit FKN overexpression and also suppresses inflammation development in a SAP rat model. More importantly, this study indicated that FKN, which is overexpressed in the SAP rat model, may serve as a novel and effective therapeutic target for SAP.
authors: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong                     University School of Medicine, Shanghai 200025, P.R. China.
authors: Liya
authors: L
authors: Huang
authors: Junwen
authors: J
authors: Ma
authors: Yuming
authors: Y
authors: Tang
authors: Ping
authors: P
authors: Chen
authors: Shuxian
authors: S
authors: Zhang
authors: Yongping
authors: Y
authors: Zhang
authors: Yao Zong
authors: YZ
authors: Yuan
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002108:Ceruletide / Q000494:pharmacology; D054428:Chemokine CX3CL1 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D005786:Gene Expression Regulation; D016209:Interleukin-8 / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000097:blood; D019283:Pancreatitis, Acute Necrotizing / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054428:Chemokine CX3CL1; D016209:Interleukin-8; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide; D045022:Lactate Dehydrogenases; D000681:Amylases