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- W4313373135 abstract "Abstract Chronic inflammation is associated with several disorders and therefore the identification of novel regulators of inflammation is needed. We identified GLI3 as a novel component of the TLR-TRIF signaling. Stimulation of monocytes with LPS increased GLI3 expression in a hedgehog-independent mechanism. We stimulated cells with MPLA, (TLR4 ligand that signals through TRIF) and polyI:C (TLR3 ligand) and found that IRF3 directly binds to the GLI3 promoter and IRF3 increased GLI3 expression. We generated a conditional knockout (cko) mouse where GLI3 was deleted in myeloid cells using LysM-Cre mediated recombination. IFA-elicited macrophages from cko mice stimulated with LPS showed reduced IL-6, CCL2 and TNF-a secretion compared to macrophages from wild-type (wt) littermates. We also performed RNA sequencing of LPS treated or untreated macrophages from GLI3 cko or wt mice. Using a generalized linear model in edgeR, we identified 495 genes with significant interaction effects between genotype and LPS treatment. Ingenuity Pathway Analysis of the interaction genes revealed “Inflammatory Response” and “Immune Cell Trafficking” pathways as most significantly enriched. The 25 significant interaction genes on these pathways included 9 with a positive interaction (Ccl25, Cd226, Cgas, Hmgn5, Il12b, Lrrc8a, Rapgef3, Rnf122, and Tlr8) and 16 with a negative interaction (Acacb, Adipoq, Ccl1, Ccne1, Cx3cl1, Fry, Gstk1, Mertk, Nqo2, Slc6a4, Sort1, Timd4, Tnfrsf18/GITR, Tnfsf13/APRIL, Tnfsf13b/BAFF, and Trem2). Taken together, these results identify a novel role for GLI3 in mediating TLR-TRIF-induced inflammation and identify a novel set of inflammatory genes that are dependent on GLI3 in response to TLR-TRIF signaling." @default.
- W4313373135 created "2023-01-06" @default.
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- W4313373135 date "2020-05-01" @default.
- W4313373135 modified "2023-09-27" @default.
- W4313373135 title "TLR-TRIF signaling induces GLI3 to modulate inflammation" @default.
- W4313373135 doi "https://doi.org/10.4049/jimmunol.204.supp.152.5" @default.
- W4313373135 hasPublicationYear "2020" @default.
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