title: Activin A inhibits activities of lipopolysaccharide-activated macrophages via TLR4, not of TLR2.
abstract: Activin A, a member of TGF-β superfamily, is involved in either pro-inflammatory or anti-inflammatory responses. Our previous studies have reported that lipopolysaccharide (LPS) can simulate activin A secretion from macrophage, and activin A can induce rest macrophage activation in mice, but inhibit the activities of the activated macrophages. However, the relationship of activin and LPS actions and their mechanism are not well characterized. In the present study, the results showed that both activin A and LPS promoted the phagocytic activities of mouse peritoneal macrophages in vivo and in vitro, but activin A inhibited the phagocytosis of LPS-activated macrophages. Simultaneously, the results revealed that activin A inhibited the Toll-like receptor 4 (TLR4) expression on LPS-activated mouse peritoneal macrophages in vivo and in vitro, whereas there was no obvious change of TLR2 expression. Moreover, the results showed that activin A obviously reduced the TLR4 mRNA and protein expressions in LPS-activated macrophage cell line RAW264.7 cells, and the inhibitory effect of activin A on the TLR4 expression was significantly attenuated in Smad3 knock-down RAW264.7 cells. Interestingly, LPS promoted the expression of activin type IIA receptor (ActRIIA) on mouse peritoneal macrophages in vivo, and also up-regulated ActRIIA and activin signal molecules Smad2, 3 mRNA expressions. These data suggest that activin A inhibits LPS action on macrophages in vivo via suppressing TLR4 expression, and LPS further augments the negative feedback action of activin A via up-regulating activin signaling transduction.
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xueling
authors.initials: X
authors.lastname: Cui
authors.forename: Jingyan
authors.initials: J
authors.lastname: Ge
authors.forename: Jiru
authors.initials: J
authors.lastname: Li
authors.forename: Liman
authors.initials: L
authors.lastname: Niu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Liu
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D028341:Activins / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C422405:activin A; D028341:Activins