PLoS ONE (Apr 2011)

Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation.

  • Tatsukuni Ohno,
  • Keisuke Oboki,
  • Hideaki Morita,
  • Naoki Kajiwara,
  • Ken Arae,
  • Shizuko Tanaka,
  • Masako Ikeda,
  • Motoyasu Iikura,
  • Taishin Akiyama,
  • Jun-ichiro Inoue,
  • Kenji Matsumoto,
  • Katsuko Sudo,
  • Miyuki Azuma,
  • Ko Okumura,
  • Thomas Kamradt,
  • Hirohisa Saito,
  • Susumu Nakae

DOI
https://doi.org/10.1371/journal.pone.0018404
Journal volume & issue
Vol. 6, no. 4
p. e18404

Abstract

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BackgroundIL-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.Methodology/principal findingsTo 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/significanceOur findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-derived paracrine IL-33 stimulation.