Anti-inflammatory effects of high-dose IgG on TNF-α-activated human coronary artery endothelial cells

European Journal of Immunology
Akio MatsudaJun Abe

Abstract

High-dose infusion of IgG (IVIG) is used to treat autoimmune and inflammatory diseases, including Kawasaki disease (KD). Although the immunomodulatory effects of IVIG on blood cells such as macrophages have been well studied, its effects on tissue cells remain unclear. Here, we show that high-dose IgG specifically and completely inhibited TNF-α-induced, but not IL-1β-induced, secretion of proinflammatory cytokines such as G-CSF and IL-6 by cultured human coronary artery endothelial cells (HCAECs). High-dose IgG did not inhibit TNF-α-mediated early signaling events of the NF-κB and MAPK pathways but it potently inhibited gene expression of G-CSF and IL-6 12 h after TNF-α-stimulation. Interestingly, suppression of the G-CSF and IL-6 gene expression correlated closely with functional inhibition of a transcription factor, C/EBPδ, whose binding sites in the promoters of G-CSF and IL-6 have been shown to be critical for their transcriptional activation. Furthermore, the inhibitory effect of intact IgG on HCAECs was exerted mainly via its F(ab')(2) fragment, and not its Fc fragment. These findings suggest that the clinical effects of IVIG on KD patients are at least in part due to its direct anti-inflammatory effects on the coronary e...Continue Reading

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Citations

Mar 1, 2013·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Jun Abe, Akio Matsuda
Mar 26, 2014·American Journal of Respiratory Cell and Molecular Biology·Hirotoshi UnnoAkio Matsuda
Feb 16, 2020·European Journal of Clinical Investigation·Fei Fei LiuPeng Hu
Apr 4, 2016·The Journal of Pediatrics·Yumi KoikeTsukasa Higuchi

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