Signal pathways in astrocytes activated by cross-talk between of astrocytes and mast cells through XXXX - @entity4458 .

@entity1 @entity3007 @entity6504 @entity20821 @entity19 @entity3721 @entity14636 @entity4458 @entity56 @entity463 @entity34901 @entity179 @entity141 @entity16279 @entity15
BACKGROUND: Astrocytes, which play an active role in chronic inflammatory diseases like @entity15 , exist close to mast cells with which they share perivascular localization. We previously demonstrated the possibility that astrocytes and mast cells interact in vitro and in vivo. This study aimed to investigate the signaling pathways and the role for astrocytes in the interaction of astrocytes and mast cells. METHODS: We co-cultured @entity1 U87 @entity463 (U87) and @entity1 mast cell-1 (HMC-1) cell lines, and @entity19 cerebral cortices-derived astrocytes and @entity19 bone marrow-derived mast cells (BMMCs). Intracellular @entity141 ([ @entity141 ]i) was measured by confocal microscopy; @entity14636 siRNA by Silencer Express Kit; small GTPases by @entity3007 -pull down assay; PKCs, MAPKs, @entity14636 , @entity4458 , @entity34901 , @entity16279 , @entity3721 ( @entity3721 ) by Western blot; NF-kB and AP-1 by EMSA; cytokines by RT-PCR. An @entity56 ( @entity56 ) model was induced using @entity6504 ( @entity6504 ) peptide and pertussis toxin in @entity19 . Co-localization of @entity3721 and astrocytes in @entity56 brain tissues was determined by immunohistochemistry. RESULTS: Each astrocyte co-culture had increases in [ @entity141 ]i levels, release of cytokines and chemokines; activities of Rho-family GTPases, NF-kB/AP-1/STAT1727, and Jack1/2, STAT1701. These effects were inhibited by anti- @entity14636 antibody or @entity14636 siRNA, and signaling pathways for @entity34901 were inhibited by anti- @entity3721 antibody. @entity56 score, expression of @entity3721 , and co-localization of @entity3721 and astrocytes were enhanced in brain of the @entity56 model. Anti- @entity14636 antibody or @entity20821 pretreatment reduced these effects in @entity56 model. CONCLUSIONS: These data suggest that astrocytes activated by the @entity14636 - @entity4458 interaction in co-culture induce inflammatory cytokine production via small GTPases, and the secreted cytokines re-activate astrocytes via Jak/STAT1701 pathways, and then release more cytokines that contribute to exacerbating the development of @entity56 . These findings imply that the pro-inflammatory mediators produced by cell-to-cell cross-talk via interaction of @entity14636 - @entity4458 may be as a promising therapeutic target for @entity179 like @entity15 .
