title: Activated endothelial cells limit inflammatory response, but increase chemoattractant potential and bacterial clearance by human monocytes.
abstract: Inflammation is the normal immune response of vascularized tissues to damage and bacterial products, for which leukocyte transendothelial migration (TEM) is critical. The effects of cell-to-cell contact seen in both leukocyte and endothelial cells include cytoskeleton rearrangement, and dynamic expression of adhesion molecules and metalloproteinases. TEM induces expression of anti-apoptotic molecules, costimulatory molecules associated with antigen presentation, and pattern recognition receptors (PRR), such as TLR-4, in monocytes. However, little is known about how TLR-4 increment operates in monocytes during an inflammatory response. To understand it better, we used an in vitro model in which monocytes crossed a layer of IL-1β stimulated Human Umbilical Vein Endothelial Cells (HUVEC). After TEM, monocytes were tested for the secretion of inflammatory cytokines and chemokines, their phenotype (CD14, CD16, TLR-4 expression), and TLR-4 canonical [Nuclear Factor kappa B, (NF-κB) pathway] and non-canonical [p38, extracellular signal-regulated kinases (ERK) 1/2 pathway] signal transduction induced by lipopolysaccharide (LPS). Phagocytosis and bacterial clearance were also measured. There was diminished secretion of LPS-induced inflammatory cytokines (IL-1β, IL-6, and TNF-α) and higher secretion of chemokines (CXCL8/IL-8 and CCL2/MCP-1) in supernatant of TEM monocytes. These changes were accompanied by increases in TLR-4, CD14 (surfaces expression), p38, and ERK1/2 phosphorylated cytoplasmic forms, without affecting NF-κB activation. It also increased bacterial clearance after TEM by an O2 -independent mechanism. The data suggest that interaction between endothelial cells and monocytes fine-tunes the inflammatory response and promotes bacterial elimination.
authors.affiliation: Graduate Program on Immunology, ENCB-IPN, Mexico City, Mexico.|Medical Research Unit on Immunochemistry, Specialties Hospital of the National Medical Centre "Siglo XXI" Mexican Social Security Institute (IMSS), Mexico City, Mexico.
authors.forename: Ismael
authors.initials: I
authors.lastname: Mancilla-Herrera
authors.affiliation: Medical Research Unit in Thrombosis, Hemostasis and Atherogenesis, Regional General Hospital Dr. Carlos MacGregor Sánchez Navarro, IMSS, Mexico City, Mexico.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Alvarado-Moreno
authors.affiliation: Education and Research Division, Woman Hospital, Health Ministry, Mexico City, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Cérbulo-Vázquez
authors.affiliation: Medical Research Unit on Immunochemistry, Specialties Hospital of the National Medical Centre "Siglo XXI" Mexican Social Security Institute (IMSS), Mexico City, Mexico.|Graduate Program on Chemical and Biological Sciences, ENCB-IPN, Mexico City, Mexico.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Prieto-Chávez
authors.affiliation: Gastrointestinal Surgery Service, Specialties Hospital of the National Medical Centre "Siglo XXI", IMSS, Mexico City, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ferat-Osorio
authors.affiliation: Medical Research Unit on Immunochemistry, Specialties Hospital of the National Medical Centre "Siglo XXI" Mexican Social Security Institute (IMSS), Mexico City, Mexico.
authors.forename: Constantino
authors.initials: C
authors.lastname: López-Macías
authors.affiliation: Molecular Immunology Laboratory, Immunology Department, ENCB-IPN, Mexico City, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada-Parra
authors.affiliation: Medical Research Unit on Immunochemistry, Specialties Hospital of the National Medical Centre "Siglo XXI" Mexican Social Security Institute (IMSS), Mexico City, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Isibasi
authors.affiliation: Medical Research Unit on Immunochemistry, Specialties Hospital of the National Medical Centre "Siglo XXI" Mexican Social Security Institute (IMSS), Mexico City, Mexico.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Arriaga-Pizano
mesh_terms: D018925:Chemokines / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D050296:Microbial Viability / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology*; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018925:Chemokines; D002630:Chemotactic Factors; D018950:Lipopolysaccharide Receptors; D051197:Toll-Like Receptor 4; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Inflammation; bacterial clearance; chemokines; cytokines; phagocytosis; transendothelial migration