Sung Kyu Park

Myeloid-derived suppressor cells (MDSCs) regulate T cell immunity, and this population is a new therapeutic target for immune regulation. A previous study showed that transforming growth factor-β (TGF-β) is involved in controlling MDSC differentiation and immunoregulatory function in vivo. However, the direct effect of TGF-β on MDSCs with various cytokines has not previously been tested. Thus, we examined the effect of various cytokine combinations with TGF-β on MDSCs derived from bone marrow ce

Previous studies showed that hepatitis B virus polymerase (HBV Pol) interacts with host factors such as the Hsp90 complex, which is a critical step in viral genome replication. In this report, we propose that another chaperone, Hsp60, interacts with human HBV Pol and that this is a very important step for maturation of human HBV Pol into the active state. In the immunoprecipitation of recombinant human HBV Pol expressed in insect cells with the recombinant baculovirus expression system, the 60-k

Chronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon α, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.2.15 cells. We find that ciclopirox, a synthetic antifungal agent, strongly inhibits HBV replication in cells and in mi

The major role of hepatitis B virus polymerase (HBV pol) is polymerization of nucleotides, but it also participates in protein priming and the packaging of its own genome into capsids. Therefore, HBV pol may require many assistance factors for its roles. Previous reports have shown that Hsp60, a molecular chaperone, activates HBV pol both in vitro and ex vivo, such as inside insect cells. Moreover, HBV pol binds to Hsp60 in the HepG2 host cell line. In this report, we show that Hsp60 plays a rol

NF-kappaB activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNF)-alpha stimulation. TNF-alpha induces apoptosis sensitive to the hepatitis B virus (HBV) infected cells, despite sustained NF-kappaB activation. Our results indicate that the HBV infection induces sustained NF-kappaB activation, in a manner similar to the TNF-alpha stimulation. However, these effects are not merely combined. Computational simulations show

Dyskerin pseudouridine synthase 1 (DKC1) is a conserved gene encoding the RNA-binding protein dyskerin, which is an essential component of the telomerase holoenzyme. DKC1 up-regulation is frequently observed in many different human cancers including hepatocellular carcinoma (HCC); however, its regulatory mechanisms remain unclear. Thus, we investigated the regulatory mechanism of DKC1 in HCC progression. We found that protein-disulfide isomerase-associated 3 (PDIA3) interacted with the DKC1 regu

Myeloid-derived suppressor cells (MDSCs) play roles in immune regulation during neoplastic and non-neoplastic inflammatory responses. This immune regulatory function is directed mainly toward T cells. However, MDSCs also regulate other cell populations, including B cells, during inflammatory responses. Indeed, B cells are essential for antibody-mediated immune responses. MDSCs regulate B cell immune responses directly via expression of effector molecules and indirectly by controlling other immun

Although efficient vaccines are available, chronic hepatitis B (HBV) infection poses a major health problem worldwide, and prolonged treatment of chronically infected HBV patients with nucleoside analogs often results in drug-resistant HBV variants. Therefore, it is critical to evaluate the contribution of the HBV polymerase to mutations. FLAG-tagged wild-type (FPolE) and mutant (FPolE/D551A) HBV polymerases have been expressed in insect cells and purified. The purified FPolE showed DNA polymera

The roles of Notch1 and Notch2 in T-cell function have been well studied, but the functional roles of Notch in B cells have not been extensively investigated, except for Notch2 involvement in peripheral marginal zone B-cell differentiation. This study examined the roles of Notch1 in murine primary B cells. During B-cell activation by B-cell receptor ligation, Notch1 was up-regulated while Notch2 was not. In addition, Notch1 up-regulation itself did not contribute to the further activation of B c