LL-37, HNP-1, and HBD2/3 modulate the secretion of cytokines TNF-α, IL-6, IFN-γ, IL-10 and MMP1 in human primary cell cultures
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The aim of this study was to evaluate the effects of the LL-37, HNP-1 and HBD2/3 peptides on cytokine andMMPproduction in human polymorphonuclear cells, mononuclear cells and chondrocytes. The levels of cytokines in supernatants from mononuclear and polymorphonuclear cell cultures were measured with a cytometric bead array by flow cytometry. Likewise, the levels of metalloproteinase/MMP-1, 3, and 13 were measured in supernatants from chondrocyte cultures using an ELISA. The expression of RANKL on lymphocytes was analyzed by flow cytometry. We observed increased levels of TNF-α, IL-6 and IL-10 in mononuclear and polymorphonuclear cell cultures stimulated with HBD-2/3.We also observed increased levels of IFN-γ, IL-10, and IL-6 in mononuclear cell cultures stimulated with HNP-1, and increased IL-6 levels were observed in polymorphonuclear cell cultures exposed to HNP-1. We also found that the MMP-1 level increased in the chondrocyte cultures stimulated with HBD-3, whereas the MMP-1 level was decreased in cultures exposed to LL-37. The present report is the first study to determine that HNP-1and HBD2/3 promote the secretion of pro-inflammatory cytokines by polymorphonuclear and mononuclear cells and the secretion of MMP by chondrocytes, whereas LL-37 diminishes MMP1 secretion. Our results suggest that HBD-2/3 and HNP1 might play a pathological role in rheumatoid arthritis, while LL-37 might have a protective role. © 2016 John Libbey Eurotext.
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Chondrocyte culture; Host defense peptides; Inflammatory cytokines; Matrix metalloproteinases; Neutrophil culture; Rheumatoid arthritis alpha defensin; beta defensin 2; beta defensin 3; cathelicidin antimicrobial peptide LL 37; collagenase 3; gamma interferon; human neutrophil peptide 1; interleukin 10; interleukin 6; interstitial collagenase; osteoclast differentiation factor; recombinant interleukin 1beta; stromelysin; tumor necrosis factor; unclassified drug; alpha defensin; beta defensin; cathelicidin; cathelicidin antimicrobial peptide; cytokine; DEFB4A protein, human; human neutrophil peptide 1; matrix metalloproteinase; Article; cartilage cell; controlled study; cytokine release; defense mechanism; enzyme linked immunosorbent assay; flow cytometry; gene expression regulation; host resistance; human; human cell; peripheral blood mononuclear cell; polymorphonuclear cell; primary cell culture; protein expression; rheumatoid arthritis; spectrophotometry; biosynthesis; chondrocyte; metabolism; mononuclear cell; alpha-Defensins; beta-Defensins; Cathelicidins; Chondrocytes; Cytokines; Humans; Leukocytes, Mononuclear; Matrix Metalloproteinases; Primary Cell Culture
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