title: 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.
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.
authors.affiliation: Central Research Laboratory, Research and Development Division, Japan Blood Products Organization, 8F Kobe KIMEC Center Building, 1-5-2, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan, murakami-kazuki@jbpo.or.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Murakami
authors.forename: Chiaki
authors.initials: C
authors.lastname: Suzuki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Fujii
authors.forename: Fujio
authors.initials: F
authors.lastname: Kobayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.forename: Akihito
authors.initials: A
authors.lastname: Kamizono
mesh_terms: D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide; D002460:Cell Line; D024243:HMGB1 Protein / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D011498:Protein Precursors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C000606589:CALCA protein, human; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C508600:IL6 protein, human; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D015850:Interleukin-6; D016328:NF-kappa B; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D002116:Calcitonin; D020928:Mitogen-Activated Protein Kinases; D015740:Calcitonin Gene-Related Peptide