Recombinant Mouse MCP1 (a.a. 24-96) [His]

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9(?/?)), DOCK10 (DOCK10(?/?)), or DOCK11 (DOCK11(?/?)) had been deleted and examined the phenotypic effects of these gene deletions in MOG(35?55) peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10(?/?) mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10(?/?) and DOCK11(?/?) mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10(?/?) mice. No apparent phenotype was observed for DOCK9(?/?) mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10(?/?) mice. Up-regulation of C?C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10(?/?) astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis.

Extremely low-frequency electromagnetic fields (ELF-EMFs) (1-300 Hz) have been found to have practical applications in biological research. A case in point is the effect of ELF-EMF on the regulation of cell fate. In this study, we investigated the correlation between ELF-EMF stimulation of PPAR gamma to the stemness, tumorigenicity, and invasiveness of breast cancer stem cellsin vitro.The CD44(+)/CD24(-) subpopulation of the breast CSCs was isolated from the MDA-MB-231 breast cancer cell line. The CSCs were then exposed to ELF-EMF and further assays were carried out. ELF-EMF increased the expression of PPAR gamma and other critical proteins leading to cell cycle arrest and reduced stemness as evidenced by decreased expression of stemness genes and reduced proliferation rate in ELF-EMF-exposed CSCs compared to that in nonexposed CSCs. There was a decrease in the tumor-forming and invasion ability of CSCs that were exposed to ELF-EMFs.