The results of dot blot showed that except for two patients (P5 and P8), serum CypA level decreased markedly after liver transplantation (Fig. (Fig.9B9B). FIG. 9. Increased serum CypA levels in natural HBV infections. (A) Serum CypA levels selleck chemical were compared among chronic hepatitis B patients and healthy individuals. Serum CypA was increased significantly in chronic hepatitis B patients (P < 0.01, Student t ... DISCUSSION We demonstrate here that CypA secretion can be specifically induced by SHBs expression and secretion in cells and in mice. Since both SHBs and CypA are secreted via the vesicular secretion pathway (26, 33), the interaction between SHBs and CypA, either by direct interaction or indirectly bridged by some cellular components as revealed by GST pull-down and coimmunoprecipitation assays provides a reasonable mechanism for SHBs-induced CypA secretion.
It is likely that CypA binds to SHBs and is secreted along with HBsAg particles. However, whether CypA is incorporated into the viral particles or merely bound with HBsAg or both is an interesting question that ought to be explored in the future. It is noteworthy, however, that given the large number of cellular proteins participating in the cellular secretion machinery (3), other cellular factors might also be involved in the interaction between CypA and SHBs. Details in the cosecretion of CypA-HBsAg complex remain to be further investigated. CypA is a ubiquitously and abundantly expressed cellular protein belonging to the immunophilin family (40).
It was originally identified as the receptor for immunosuppressive drug Cs (14) and was later considered an important cellular chaperone molecule (35). The CypA-Cs complex inhibits the protein phosphatase activity of calcineurin and subsequently inhibits signal transduction pathway AV-951 for initiating T-lymphocyte activation (21, 22, 40). CypA was recently found secreted from cells in response to oxidative stress (15, 33) and inflammatory stimulations (2, 17). Our results indicate that viral protein expression such as SHBs is a novel mode of triggering CypA secretion. Secreted CypA can act as a potent chemoattractant to inflammatory cells such as T cells (1), monocytes (30), eosinophils, and neutrophils (38). In the present study, we used a hydrodynamic injection mouse model to investigate the potential role of CypA played in HBsAg-related liver inflammation. Our results showed that SHBs expression in mice increased serum CypA levels, elevated serum ALT/AST levels, and caused infiltration of lymphocytes surrounding hepatocytes that expressed SHBs.