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Transcriptional profiling reveals that C 5a alters micro RNA in brain endothelial cells
Author(s) -
Eadon Michael T.,
Jacob Alexander,
Cunningham Patrick N.,
Quigg Richard J.,
Garcia Joe G. N.,
Alexander Jessy J.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12314
Subject(s) - systemic lupus erythematosus , microrna , complement system , biology , microarray analysis techniques , inflammation , neuroinflammation , microarray , immunology , central nervous system , immune system , gene expression , gene , medicine , pathology , endocrinology , genetics , disease
Summary Blood–brain barrier ( BBB ) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus ( SLE ). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB . Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (mi RNA ) altered in mouse brain endothelial cells (b E nd3) by lupus serum and the complement protein, C 5a. Of the 318 mi RNA evaluated, 23 mi RNA s were altered by lupus serum and 32 were altered by C 5a alone compared with controls. Seven mi RNA s ( P < 0·05) were differentially expressed by both treatments: mmu‐mi R ‐133a*, mmu‐mi R ‐193*, mmu‐mi R ‐26b, mmu‐mi R ‐28*, mmu‐mi R ‐320a, mmu‐mi R ‐423‐3p and mmu‐mi R ‐509‐5p. The microarray results were validated by quantitative RT ‐ PCR . In line with the in vitro results, expression of mi R ‐26b and mi R ‐28* were also significantly up‐regulated in lupus mouse brain which was reduced by C 5a receptor inhibition. Target prediction analysis revealed mi R gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the mi RNA s reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings.