The Inflammatory and Fibrotic Patterns of Hepatic Stellate Cells Following Coagulation Factors (VII or X)-Shielded Adenovirus Infection.

The role of coagulation factors on the inflammatory effect of adenovirus (Ad) is an unresolved question that was considered herein. Adenovirus-36(Ad36) and adenovector-5-GFP(Ad5-GFP) were prepared; then, they were loaded with VII or FX factors. The size/charge parameters and transduction efficiency were evaluated using fluorescent microscopy and Zetasizer, respectively. The Ad36-coagulation factor complexes were added on the stellate cells, LX-2. Thereafter, the expression levels of inflammatory and fibrotic genes including PKR, IL-1β, TNF-α, TIMP-1, collagen, and TGF-β were measured by qPCR and ELISA assays. The loading of FVII or FX factors not only increased the size/charge of Ad5-GFP but also enhanced the transduction rate up to 60% and 75%, respectively, compared to the controls (45%). The PKR expression analysis showed an upregulation following treatment with all Ad36 forms (P = 0.0152). The IL-1β and TNF-α cytokines analyses demonstrated that the Ad36-FVII complex elicited the highest inflammatory response (P = 0.05). Similarly, the fibrosis-related expression analysis revealed a more inductive role of FVII when loaded on Ad36, compared to the FX factor. The findings suggested that adenovirus elicited the innate inflammatory and activation state in the hepatic stellate cell. In addition, adenovirus shielded by FVII exhibited more innate inflammation as well as activation of the stellate cells than the FX-loaded virus.