title: 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.
abstract: The aim of this study was to evaluate the effects of the LL-37, HNP-1 and HBD2/3 peptides on cytokine and MMP production 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.
authors.affiliation: Medical Research Unit of Zacatecas, Mexican Institute of Social Security, Zacatecas, Mexico.
authors.forename: Carlos Erik
authors.initials: CE
authors.lastname: Medina Santos
authors.affiliation: Medical Research Unit of Zacatecas, Mexican Institute of Social Security, Zacatecas, Mexico.
authors.forename: Carmen Nathaly
authors.initials: CN
authors.lastname: López Hurtado
authors.affiliation: Medical Research Unit of Zacatecas, Mexican Institute of Social Security, Zacatecas, Mexico.
authors.forename: Bruno
authors.initials: B
authors.lastname: Rivas Santiago
authors.affiliation: Research Center for Health Sciances and Medicine, San Luis Potosí, México.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gonzalez-Amaro
authors.affiliation: Medical Research Unit of Zacatecas, Mexican Institute of Social Security, Zacatecas, Mexico.
authors.forename: Yolanda Guadalupe
authors.initials: YG
authors.lastname: Cataño Cañizales
authors.affiliation: Faculty of Chemical Sciences, Autonomous University of Zacatecas, Zacatecas, Mexico.
authors.forename: Margarita de la Luz
authors.initials: ML
authors.lastname: Martínez Fierro
authors.affiliation: Medical Research Unit of Zacatecas, Mexican Institute of Social Security, Zacatecas, Mexico.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Enciso-Moreno
authors.affiliation: Medical Research Unit of Zacatecas, Mexican Institute of Social Security, Zacatecas, Mexico.
authors.forename: Mariana Haydee
authors.initials: MH
authors.lastname: García Hernández
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D061251:Primary Cell Culture; D023084:alpha-Defensins / Q000378:metabolism*; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; C106641:DEFB4A protein, human; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1; D020782:Matrix Metalloproteinases
keywords: chondrocyte culture; host defense peptides; inflammatory cytokines; matrix metalloproteinases; neutrophil culture; rheumatoid arthritis