Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Secreted filarial nematode galectins modulate host immune cells

Abstract: Lymphatic filariasis (LF) is a mosquito-borne disease caused by filarial nematodes including Brugia malayi. Over 860 million people worldwide are infected or at risk of infection in 72 endemic countries. The absence of a protective vaccine means that current control strategies rely on mass drug administration programs that utilize inadequate drugs that cannot effectively kill adult parasites, thus established infections are incurable. Progress to address deficiencies in the approach to LF control is hindered by a poor mechanistic understanding of host-parasite interactions, including mechanisms of host immunomodulation by the parasite, a critical adaptation for establishing and maintaining infections. The canonical type 2 host response to helminth infection characterized by anti-inflammatory and regulatory immune phenotypes is modified by filarial nematodes during chronic LF. Current efforts at identifying parasite-derived factors driving this modification focus on parasite excretory-secretory products (ESP), including extracellular vesicles (EVs). We have previously profiled the cargo of B. malayi EVs and identified B. malayi galectin-1 and galectin-2 as among the most abundant EV proteins. In this study we further investigated the function of these proteins. Sequence analysis of the parasite galectins revealed highest homology to mammalian galectin-9 and functional characterization identified similar substrate affinities consistent with this designation. Immunological assays showed that Bma-LEC-2 is a bioactive protein that can polarize macrophages to an alternatively activated phenotype and selectively induce apoptosis in Th1 cells. Our data shows that an abundantly secreted parasite galectin is immunomodulatory and induces phenotypes consistent with the modified type 2 response characteristic of chronic LF infection.

77Se-Enriched Selenoglycoside Enables Significant Enhancement in NMR Spectroscopic Monitoring of Glycan–Protein Interactions

Abstract: Detailed investigation of ligand–protein interactions is essential for better understanding of biological processes at the molecular level. Among these binding interactions, the recognition of glycans by lectins is of particular importance in several diseases, such as cancer; therefore, inhibition of glycan-lectin/galectin interactions represents a promising perspective towards developing therapeutics controlling cancer development. The recent introduction of 77Se NMR spectroscopy for monitoring the binding of a selenoglycoside to galectins prompted interest to optimize the sensitivity by increasing the 77Se content from the natural 7.63% abundance to 99%. Here, we report a convenient synthesis of 77Se-enriched selenodigalactoside (SeDG), which is a potent ligand of the medically relevant human galectin-3 protein, and proof of the expected sensitivity gain in 2D 1H, 77Se correlation NMR experiments. Our work opens perspectives for adding isotopically enriched selenoglycans for rapid monitoring of lectin-binding of selenated as well as non-selenated ligands and for ligand screening in competition experiments.

The role of galectin-3 and galectin-9 in the chronic inflammation of rheumatoid arthritis

Abstract: Fibroblasts are important regulators of inflammatory processes. The phenotype of fibroblasts differ according to anatomical site which may dtermine immune functions such as leukocyte accumulation and predilection for inflammatory disease in certain tissues. This thesis describes the expression profile and explores the function of a family of immunomodulatory proteins (galectins) in fibroblasts from rhematoid arthritis patients. Synovial fibroblasts were found to differ significantly from bone marrow and skin fibroblasts with higher expression of galectin-9 and galectin-12 in synovial fibroblasts. Galectin-9 and galectin-3 expression was also examined in situ in synovial tissue from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Expression of both galectins were higher in RA synovial tissue compared to OA but not in synovial fibroblasts cultured in vitro. Galectin-3 expression seemed to be controlled by epigenetic factors (methylation) but not cytokine stimulation. Galectin-9 production was up-regulated by interferon-y, interleukin-1b and ligands for Toll-like receptors 3 (TLR3) and 4 (TLR4). It was found that intracellular presence of galectin-9 in RA synovial firboblasts increased their resistance to apoptosis. Galectin-3 level are increased in teh joints of patients with rheumatoid arthritis. Studies on the effect and mechanism of galectin-3 action on fibroblasts revealed that exogenously added galectin-3 induced production of cytokines (IL-6) from synovial and skin fibroblasts but the production of moncyte attracting chemokines (CCL5, CCL2) was induced uniquely in fibroblasts derived from teh synovium. Different signalling pathways mediated the secretion of those mediators. IL-6 release depended on MAP kinases p38, ERK and JNK as well as NFkB transcription factor, whereas CCL5 production required PI3/Akt and NFkB