Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 369, Issue 4, pp 428–433 | Cite as

Intravenous immunoglobulin inhibits NF-κB activation and affects Fcγ receptor expression in monocytes/macrophages

  • Takashi Ichiyama
  • Yoshiko Ueno
  • Masanari Hasegawa
  • Akihiro Niimi
  • Tomoyo Matsubara
  • Susumu Furukawa
Original Article

Abstract

High-dose intravenous immunoglobulin (IVIG) therapy is well established as a standard therapy for Kawasaki disease (KD) that reduces the risk of developing coronary artery aneurysms. Activation of monocytes/macrophages and tumor necrosis factor-α (TNF-α) activity are responsible for severe vascular injury in acute KD. We examined whether or not IVIG inhibits TNF-α-induced activation of transcription factor NF-κB, a factor that is essential for the expression of proinflammatory cytokines, in human monocytic U-937 cells. The inhibitory effect of IVIG on NF-κB activation induced by TNF-α was evaluated by Western blotting and flow cytometry. In addition, we examined the effect of IVIG on the expression of FcγIII (CD16) and FcγRIIb (CD32b) in U-937 cells and peripheral blood CD14+ monocytes/macrophages by flow cytometry. Western blotting demonstrated that IVIG inhibits NF-κB activation in U-937 cells, and flow cytometry that IVIG inhibits NF-κB activation in U-937 cells in a dose-related manner. Western blotting of cytoplasmic extracts of U-937 cells revealed that IVIG inhibited degradation of the IκBα protein. Moreover, flow cytometry demonstrated that IVIG decreased the expression of FcγRIII in U-937 cells and peripheral blood CD14+ monocytes/macrophages. However, Western blotting revealed that IVIG did not affect the quantity of FcγRIII protein, and PCR that IVIG did not affect the quantity of FcγRIII mRNA in the cells. These findings suggest that IVIG inhibits TNF-α-induced NF-κB activation in monocytes/macrophages, and blocks FcγRIII on the membranes of monocytes/macrophages.

Keywords

FcγRIIb FcγRIII Intravenous immunoglobulin Monocytes/macrophages NF-κB TNF-α 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Takashi Ichiyama
    • 1
  • Yoshiko Ueno
    • 1
  • Masanari Hasegawa
    • 1
  • Akihiro Niimi
    • 2
  • Tomoyo Matsubara
    • 1
  • Susumu Furukawa
    • 1
  1. 1.Department of PediatricsYamaguchi University School of MedicineUbe, YamaguchiJapan
  2. 2.Bayer Yakuhin Ltd.Yodogawa-ku, OsakaJapan

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