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
- 369 Downloads
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.
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.
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.
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.
KeywordsIntravenous immunoglobulin Fc fragment Procalcitonin THP-1 cells TNF-α NFκB
- 14.Shimozato T, Iwata M, Kawada H, Tamura N. Human immunoglobulin preparation for intravenous use induces elevation of cellular cyclic adenosine 3′:5′-monophosphate levels, resulting in suppression of tumour necrosis factor alpha and interleukin-1 production. Immunology. 1991;72:497–501.PubMedCentralPubMedGoogle Scholar
- 17.Murakami K, Suzuki C, Kobayashi F, Nakano A, Fujii A, Sakai K, Imada T. Intravenous immunoglobulin preparation attenuates LPS-induced production of pro-inflammatory cytokines in human monocytic cells by modulating TLR4-mediated signaling pathways. Naunyn-Schmiedebergs Arch Pharmacol. 2012;385:891–8.PubMedCrossRefGoogle Scholar
- 22.Fujii A, Kase Y, Suzuki C, Kamizono A, Imada T. An Fc gamma receptor-mediated upregulation of the production of interleukin 10 by intravenous immunoglobulin in bone-marrow-derived mouse dendritic cells stimulated with lipopolysaccharide in vitro. J Signal Transduct. 2013;2013:239320.PubMedCentralPubMedCrossRefGoogle Scholar