Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia.
BAFF is a recently identified member of the TNF ligand superfamily that plays a critical role in B cell differentiation, survival, and regulation of Ig production. In the present study, we examined whether BAFF is expressed in microglia, and the expression and release of BAFF are regulated by gangliosides. The results showed that BAFF was expressed and released in rat primary microglia as well as in BV-2 cells. Furthermore, its expression and release were increased by gangliosides stimulation and regulated by JAK-STAT, especially the STAT1- and STAT3-dependent signaling pathways. It was of particular interest to observe that SP600125 and SB203580, specific inhibitors of JNK and p38, did not inhibit BAFF synthesis but inhibited the release of sBAFF in gangliosides-treated cells by regulating furin expression, suggesting that the JNK and p38 signaling pathways regulate the release but not the synthesis of BAFF. Moreover, BV-2 cells expressed BAFF-R on their cell surface, and rat primary microglia expressed BAFF-R and TACI on their cell surface. rBAFF increased the release of cytokines, especially IL-6, TNF-alpha, and IL-10, in rat primary microglia as well as in BV-2 cells. These findings imply that BAFF secreted by microglia may play important roles in CNS inflammation by regulating microglia as well as infiltrated B cells.
Kim
Kwang Soo
KS
Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea.
Park
Ji-Young
JY
Jou
Ilo
I
Park
Sang Myun
SM
D000818:Animals; D053264:B-Cell Activating Factor / Q000096:biosynthesis* / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000187:drug effects / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045683:Furin / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology; D005911:Gliosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D016207:Cytokines; D004791:Enzyme Inhibitors; D005732:Gangliosides; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D045683:Furin