Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by soluble TGF-beta receptor type II

We have previously reported that transforming growth factor beta (TGF-beta) produced by rat hepatoma cell line KDH-8 cells suppressed the interleukin-2 (IL-2) production of T cells and the tumoricidal activity of macrophages in KDH-8 tumor-bearing rats and that the inhibition of TGF-beta production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-beta receptor type II (sTRII), namely KT1, KT2 and KT3, and one with an empty vector used as control vector (KV), and then investigated the effects of sTRII on the tumorigenicity of KDH-8 cells and immune responses in syngeneic Wistar King Aptekman/Hok (WKAH) rats. We found that sTRII expressed in sTRII transfectants could abolish growth inhibition of Mv1Lu cells by TGF-beta1 produced by the cells themselves, and that tumor growth of KT2 and KT3 clones in vivo was suppressed significantly compared with that of parent, KV and KT1 clones. Furthermore, we demonstrated that IL-2 production of splenocytes and IL12p40 mRNA expression in tumor tissues were restored in rats inoculated with KT2 and KT3 clones, whereas such restoration was not observed in rats inoculated with parent, KV and KT1 clones. Combined with a low expression of sTRII in KT1 tumor tissues, these results suggest that sTRII may to some extent be able to abolish the tumor-promoting activity of TGF-beta, and imply that sTRII might have a therapeutic effect on TGF-beta-producing tumors.     

An investig-ation into the epidemiology of chikungunya virus across neglected regions of Indonesia

BackgroundChikungunya virus (CHIKV) is an important emerging and re-emerging public health problem worldwide. In Indonesia, where the virus is endemic, epidemiological information from outside of the main islands of Java and Bali is limited.Methodology/Principal FindingsFour hundred and seventy nine acutely febrile patients presenting between September 2017–2019 were recruited from three city hospitals situated in Ambon, Maluku; Banjarmasin, Kalimantan; and Batam, Batam Island as part of a multi-site observational study. CHIKV RNA was detected in a single serum sample while a separate sample was IgM positive. IgG seroprevalence was also low across all three sites, ranging from 1.4–3.2%. The single RT-PCR positive sample from this study and 24 archived samples collected during other recent outbreaks throughout Indonesia were subjected to complete coding region sequencing to assess the genetic diversity of Indonesian strains. Phylogenetic analysis revealed all to be of a single clade, which was distinct from CHIKV strains recently reported from neighbouring regions including the Philippines and the Pacific Islands.Conclusions/SignificanceChikungunya virus strains from recent outbreaks across Indonesia all belong to a single clade. However, low-level seroprevalence and molecular detection of CHIKV across the three study sites appears to contrast with the generally high seroprevalences that have been reported for non-outbreak settings in Java and Bali, and may account for the relative lack of CHIKV epidemiological data from other regions of Indonesia.     

Localization of Tamm-Horsfall protein in chloride transporting epithelia: lack of correlation with the Na, K, Cl cotransporter

In order to test the hypothesis that Tamm-Horsfall protein (THP) and the Na, K, Cl cotransporter in chloride transporting epithelia are functionally related, the presence of THP in various rat epithelia was investigated by indirect immunocytochemical procedures. Positive staining was found in the apical cytoplasmic portion of the renal thick ascending limb, in apical large secretory granules of the pancreatic acinar cells, in the cytoplasm of the serous acinar cells of the salivary gland, and in the apical cytoplasm of mucosal cells in the jejunum. No staining was observed in the tracheal epithelial cells. These studies show that THP, or antigenically related substances, can be found in a variety of extrarenal organs. Only in the renal thick ascending limb the intracellular distribution of THP coincides partly with the distribution of the Na, K, Cl cotransporter. In all other epithelia investigated no correlation between THP staining and presence of the cotransporter was found. Thus, it seems very unlikely that Tamm-Horsfall protein and the Na, K, Cl cotransporter are functionally related.