Search

Interleukin-6 (IL-6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV) replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA) in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effects and mechanisms of all-trans retinoic acid (t-RA) on interleukin(IL)-1-induced production of several inflammatory mediators in human chondrocytes. The cartilage from OA patients receiving total knee or total hip replacement was obtained and chondrocytes were prepared. Chemokine concentrations were measured by ELISA. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined by Western blotting and/or RT/PCR. Nitrite levels were measured by Griess assays. The DNA-binding activity and transcriptional activity of activator protein-1 (AP-1) were measured by electrophoresis mobility shift assay and luciferase assay. We showed that t-RA suppressed IL-1-induced release of chemokines, including regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein-1alpha (MIP-1α) and MIP-1β. Four different retinoid derivatives all preserved inhibitory effects albeit the potency was different. t-RA potently suppressed IL-1-induced expression of iNOS and COX-2 and production of nitric oxide and prostaglandin E2. In consistent with the results in primary chondrocytes, t-RA down-regulated IL-1-induced AP-1 DNA binding activity and transcriptional activity in a human fibroblast-like (commercially labeled as chondrocyte) cell line. By examining the effect of a c-jun N-terminal kinase (JNK) specific inhibitor, we showed that the suppression of JNK-AP-1 signaling was enough to inhibit IL-1-induced production of chemokines and activation of iNOS and COX-2 pathways. Collectively, our results raise a therapeutic option that intra-articular administration of retinoid derivatives at 10-1000 nanomolar concentrations may be effective to suppress the progression of inflammatory OA. [ABSTRACT FROM AUTHOR]