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Inflammation Research

, Volume 63, Issue 9, pp 711–718 | Cite as

Intravenous immunoglobulin preparation prevents the production of pro-inflammatory cytokines by modulating NFκB and MAPKs pathways in the human monocytic THP-1 cells stimulated with procalcitonin

  • Kazuki Murakami
  • Chiaki Suzuki
  • Akihiro Fujii
  • Fujio Kobayashi
  • Atsushi Nakano
  • Akihito Kamizono
Original Research Paper

Abstract

Objective

In the previous investigations, we showed that intravenous immunoglobulin (IVIG) prevented cytokine release in procalcitonin (PCT)-stimulated monocytic cells. The aim of the present study was to investigate the underlying mechanisms of inhibition of IVIG on cytokine production in PCT-stimulated THP-1 cells.

Methods

THP-1 cells treated with phorbol myristate acetate were stimulated with PCT. The protein levels of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high-mobility group box 1 (HMGB1)] in the culture supernatants were determined using enzyme-linked immunosorbent assay kits. The mRNA level of TNF-α was determined by reverse transcription-polymerase chain reaction. The phosphorylations of nuclear factor kappa B (NFκB) and the mitogen-activated protein kinases (MAPKs) were determined by Western blotting.

Results

IVIG reduced mRNA expression and protein production of TNF-α in PCT-stimulated THP-1 cells. Not only IVIG but also both the Fc fragment and the F(ab’)2 fragment inhibited PCT-induced TNF-α, IL-6, and HMGB1 production. Furthermore, IVIG and its fragments suppressed PCT-induced phosphorylations of NFκB, p38 MAPK, and c-Jun N-terminal kinase.

Conclusions

Our results indicate that IVIG prevents PCT-induced cytokine production mediated by not only the Fab region but also the Fc region. The activity of IVIG and its fragments might be regulated by inhibiting NFκB and MAPKs pathways in THP-1 cells.

Keywords

Intravenous immunoglobulin Fc fragment Procalcitonin THP-1 cells TNF-α NFκB 

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Kazuki Murakami
    • 1
  • Chiaki Suzuki
    • 1
  • Akihiro Fujii
    • 1
  • Fujio Kobayashi
    • 1
  • Atsushi Nakano
    • 1
  • Akihito Kamizono
    • 1
  1. 1.Central Research Laboratory, Research and Development DivisionJapan Blood Products OrganizationKobeJapan

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