siRNA-based targeting of fractalkine overexpression suppresses inflammation development in a severe acute pancreatitis rat model

Huang,Liya; Ma,Junwen; Tang,Yuming; Chen,Ping; Zhang,Shuxian; Zhang,Yongping; Yuan,Yao  Zong

doi:10.3892/ijmm.2012.1050

siRNA-based targeting of fractalkine overexpression suppresses inflammation development in a severe acute pancreatitis rat model

Authors:
- Liya Huang
- Junwen Ma
- Yuming Tang
- Ping Chen
- Shuxian Zhang
- Yongping Zhang
- Yao Zong Yuan
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Affiliations: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Published online on: June 29, 2012 https://doi.org/10.3892/ijmm.2012.1050
Pages: 514-520

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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.

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