TLR-Induced SMPD3 Defects Enhance Inflammatory Response of B Cell and Macrophage in the Pathogenesis of SLE

Autor:	Yayi Hou, Jianjian Ji, Hongye Fan, Huimin Yue, Xiaojing Li, Ming You, Fei Liu, Liang Ding
Rok vydání:	2017
Předmět:	0301 basic medicine Mice Inbred MRL lpr medicine.medical_treatment Immunology Gene Expression Golgi Apparatus Apoptosis Sphingomyelin phosphodiesterase Biology Models Biological Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Ceramide kinase medicine Animals Humans Lupus Erythematosus Systemic Macrophage skin and connective tissue diseases B cell B-Lymphocytes Sphingolipids Macrophages Toll-Like Receptors General Medicine Sphingolipid Mice Inbred C57BL Disease Models Animal Sphingomyelin Phosphodiesterase 030104 developmental biology Cytokine medicine.anatomical_structure Female Signal transduction Signal Transduction 030215 immunology
Zdroj:	Scandinavian Journal of Immunology. 86:377-388
ISSN:	0300-9475
DOI:	10.1111/sji.12611
Popis:	B lymphocyte and macrophages may contribute to SLE pathogenesis through cytokine production after TLR stimulation. Emerging evidences suggested that defects of sphingolipid metabolism were responsible for SLE pathogenesis. However, it is not clear whether these defects exist in B cells and macrophages under SLE condition and whether TLR signalling pathway was related to the dysfunction of sphingolipid metabolism in SLE. Here, we demonstrated that the enzymes involved in the sphingolipid metabolism expressed abnormally in B cells from SLE patients and lupus-prone mice. Moreover, we found that TLR signalling induced the abnormal expression of sphingomyelin phosphodiesterase 3 (SMPD3), sphingosine-1-phosphate phosphatase 2 (SGPP2), ceramide kinase (CERK) and UDP glycosyltransferase 8 (UGT8), which were involved in sphingolipid metabolism. TLR signalling also induced the transportation of SMPD3 from Golgi apparatus. Furthermore, the dysfunction of SMPD3 enhanced TLR-induced inflammatory response of B cells and macrophages in turn. Thus, these findings provide an innovative direction and a new target for research and treatment of SLE.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b1f0635b977d5fe9a22cbf4c5d7efb9 https://doi.org/10.1111/sji.12611 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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