The Regulation of MS-KIF18A Expression and Cross Talk with Estrogen Receptor

This study provides a novel view on the interactions between the MS-KIF18A, a kinesin protein, and estrogen receptor alpha (ERα) which were studied in vivo and in vitro. Additionally, the regulation of MS-KIF18A expression by estrogen was investigated at the gene and protein levels. An association between recombinant proteins; ERα and MS-KIF18A was demonstrated in vitro in a pull down assay. Such interactions were proven also for endogenous proteins in MBA-15 cells were detected prominently in the cytoplasm and are up-regulated by estrogen. Additionally, an association between these proteins and the transcription factor NF-κB was identified. MS-KIF18A mRNA expression was measured in vivo in relation to age and estrogen level in mice and rats models. A decrease in MS-KIF18A mRNA level was measured in old and in OVX-estrogen depleted rats as compared to young animals. The low MS-KIF18A mRNA expression in OVX rats was restored by estrogen treatment. We studied the regulation of MS-KIF18A transcription by estrogen using the luciferase reporter gene and chromatin immuno-percipitation (ChIP) assays. The luciferase reporter gene assay demonstrated an increase in MS-KIF18A promoter activity in response to 10−8 M estrogen and 10−7M ICI-182,780. Complimentary, the ChIP assay quantified the binding of ERα and pcJun to the MS-KIF18A promoter that was enhanced in cells treated by estrogen and ICI-182,780. In addition, cells treated by estrogen expressed higher levels of MS-KIF18A mRNA and protein and the protein turnover in MBA-15 cells was accelerated. Presented data demonstrated that ERα is a defined cargo of MS-KIF18A and added novel insight on the role of estrogen in regulation of MS-KIF18A expression both in vivo and in vitro

Distribution of IgG subclasses in antimonial unresponsive Indian kala-azar patients

Sodium antimony gluconate (SAG) is the mainstay of treatment for visceral leishmaniasis (VL) or kala-azar. In view of the increasing incidence of refractoriness to SAG in India, we compared the levels of parasite-specific IgG and IgG subclasses in 20 longitudinally followed up kala-azar patients. In both SAG-responsive (n = 10) and unresponsive patients (n = 10), the levels of total IgG, IgG1, IgG2, IgG3 and IgG4 were increased, the rank order being IgG1 > IgG2 > IgG3 = IgG4. Following treatment, a significant decrease in total IgG and the four subclasses occurred in the SAG-responsive group, whereas in the SAG-unresponsive group these levels were unchanged or slightly increased. Therefore, monitoring of IgG1 and IgG2 levels in Indian kala-azar patients is a good serologic alternative to monitoring the disease status