title: Follistatin-related protein/follistatin-like 1 evokes an innate immune response via CD14 and toll-like receptor 4.
abstract: Follistatin-related protein (FRP)/follistatin-like 1 (FSTL1) has multi-specific binding nature especially with TGF-β superfamily proteins, and thereby modulates organ development. However, its function in immune systems remains unclear. Previously, we reported FRP interacts with CD14, which is known to mediate toll-like receptor 4 (TLR4) signaling. Here, we investigated whether FRP activates TLR4 signaling. Recombinant FRP induced interleukin 6 or interleukin 8 production from target cells in a CD14- and TLR4-dependent manner. Moreover, similar to lipopolysaccharide (LPS), FRP induced tolerance to the second LPS stimulation. FRP has the function of evoking innate immune responses as one of the endogenous TLR4 agonists.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Murakami
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Usui
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawabata
authors.forename: Aoi
authors.initials: A
authors.lastname: Shiomi
authors.forename: Mikiko
authors.initials: M
authors.lastname: Iguchi-Hashimoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shimizu
authors.forename: Naoichiro
authors.initials: N
authors.lastname: Yukawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Yoshifuji
authors.forename: Takaki
authors.initials: T
authors.lastname: Nojima
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umehara
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
mesh_terms: D000818:Animals; D038702:Follistatin-Related Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D038702:Follistatin-Related Proteins; C448720:Fstl1 protein, mouse; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C448799:FSTL1 protein, human