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

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.