title: Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation.
abstract: BACKGROUND
  IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to differ between ST2-deficient mice and soluble ST2-Fc fusion protein-treated mice. Even in anti-ST2 antibody (Ab)-treated mice, the phenotypes differed between distinct Ab clones, because the characterization of such Abs (i.e., depletion, agonistic or blocking Abs) was unclear in some cases.
  
  
  RESULTS
  To elucidate the precise role of IL-33, we newly generated neutralizing monoclonal Abs for IL-33. Exogenous IL-33 potentiated LPS-mediated cytokine production by macrophages. That LPS-mediated cytokine production by macrophages was suppressed by inhibition of endogenous IL-33 by the anti-IL-33 neutralizing mAbs.
  
  
  CONCLUSIONS
  Our findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-derived paracrine IL-33 stimulation.
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Tatsukuni
authors.initials: T
authors.lastname: Ohno
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oboki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.forename: Naoki
authors.initials: N
authors.lastname: Kajiwara
authors.forename: Ken
authors.initials: K
authors.lastname: Arae
authors.forename: Shizuko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masako
authors.initials: M
authors.lastname: Ikeda
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Iikura
authors.forename: Taishin
authors.initials: T
authors.lastname: Akiyama
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Inoue
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D013864:Thioglycolates / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D008070:Lipopolysaccharides; D048029:TNF Receptor-Associated Factor 6; D013864:Thioglycolates