Germinal centers (GCs) are sites of rapid B-cell proliferation and somatic mutation. These ovoid structures develop within the center of follicles and grow to a stereotypic size. The cell migration and interaction dynamics underlying GC B-cell selection events are currently under intense scrutiny. In recent study, we identified a role for a migration inhibitory receptor, S1PR2, in promoting GC B-cell confinement to GCs. S1PR2 also dampens Akt activation and deficiency in S1PR2 or components of its signaling pathway result in a loss of growth control in chronically stimulated mucosal GCs. Herein, we detail present understanding of S1PR2 and S1P biology as it pertains to GC B cells and place this information in the context of a current model of GC function.
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http://dx.doi.org/10.1111/j.1600-065X.2012.01114.x | DOI Listing |
Int J Mol Sci
December 2024
Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea.
The amount of sphingosine 1-phosphate (S1P) found in the synovial tissue of individuals with rheumatoid arthritis is five times greater than that in those with osteoarthritis. Our study aims to determine whether inhibiting S1P can mitigate collagen-induced rheumatoid arthritis (CIA) by using an S1P antagonist, JTE-013, alongside DBA-1J wild-type (WT) and knock-out (KO) mice. CIA causes increases in arthritis scores, foot swelling, synovial hyperplasia, pannus formation, proteoglycan depletion, cartilage damage, and bone erosion, but these effects are markedly reduced when JTE-013 is administered to WT mice.
View Article and Find Full Text PDFBackground: The aim of our study was to determine the role of sphingolipids, which control proliferation and apoptosis, in the placenta of pregnant women with pregnancy-associated breast cancer (PABC) after chemotherapy compared with healthy patients.
Methods: We analyzed (by the PCR method) the gene expression of key sphingolipid metabolism enzymes (sphingomyelinases (SMPD1 and SMPD3), acid ceramidase (ASAH1), ceramide synthases (CERS 1-6), sphingosine kinase1 (SPHK1), sphingosine-1-phosphate lyase 1 (SGPL1), and sphingosine-1-phosphate receptors (S1PR1, S1PR2, and S1PR3)) and the content of subspecies of ceramides, sphingosine, and sphingosine-1-phosphate in seven patients with PABC after chemotherapy and eight healthy pregnant women as a control group.
Results: We found a significant increase in the expression of genes of acid ceramidase (ASAH1), sphingosine-1-phosphate lyase 1 (SGPL1), sphingosine kinase (SPHK1), and ceramide synthases (CERS 1-3, 5, 6) in the samples of patients with PABC during their treatment with cytostatic chemotherapy.
Front Pharmacol
November 2024
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Objectives: The disruption of blood-brain barrier (BBB) is associated with poor outcomes of TBI patients. Sphingosine-1-phosphate receptor 2 (S1pr2), a member of the G protein-coupled receptor family, is involved in endothelial activation and the regulation of vascular integrity. We hypothesized that the inhibition of S1pr2 may alleviate BBB disruption and explored potential underlying molecular mechanisms.
View Article and Find Full Text PDFInt J Biol Sci
December 2024
Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Tianjin 300071, China.
Lipopolysaccharide (LPS) mediated caspases-4 (humans) and caspase-11 (rodent) (caspase-4/11) signaling can cause maturation of inflammatory cytokine IL-1β and cellular pyroptosis in the macrophages through guanylate-binding proteins (GBPs). However, how caspase-4/11s bind with GBPs together to activate caspase-4/11 by LPS remains elusive. We here found that BA derivatives from gut microbiota can regulate sensitivity of macrophages to LPS and Gram-negative bacteria through .
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
December 2024
University of Alabama at Birmingham, Birmingham, United States;
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