Author/Editor		Klein, Kerstin; Frank Bertoncelj, Mojca; Karouzakis, Emmanuel; Gay, Renate E.; Kolling, Christoph; Ciurea, Adrian; Bostanci, Nagihan; Belibasakis, Georgios N.; Lin, Lih-Ling; Distler, Oliver
Title		The epigenetic architecture at gene promoters determines cell type-specific LPS tolerance
Type		članek
Vol. and No.		, št. Vol. 83
Publication year		2017
Volume		str. 122-133
ISSN		0896-8411 - Journal of autoimmunity
Language		eng
Abstract		Synovial fibroblasts (SF) drive inflammation and joint destruction in chronic arthritis. Here we show that SF possess a distinct type of LPS tolerance compared to macrophages and other types of fibroblasts. In SF and dermal fibroblasts, genes that were non-tolerizable after repeated LPS stimulation included pro-inflammatory cytokines, chemokines and matrix metalloproteinases, whereas anti-viral genes were tolerizable. In macrophages, all measured genes were tolerizable, whereas in gingival and foreskin fibroblasts these genes were non-tolerizable. Repeated stimulation of SF with LPS resulted in loss of activating histone marks only in promoters of tolerizable genes. The epigenetic landscape at promoters of tolerizable genes was similar in unstimulated SF and monocytes, whereas the basal configuration of histone marks profoundly differed in genes that were non-tolerizable in SF only. Our data suggest that the epigenetic configuration at gene promoters regulates cell-specific LPS-induced responses and primes SF to sustain their inflammatory response in chronic arthritis.
Keywords		chronic arthritis chronic immune system stimulation synovial fibroblasts inflammation kronični artritis sinovialni fibroblast vnetje