Porphyromonas gingivalis outer membrane vesicles modulate cytokine and chemokine production by gingipain-dependent mechanisms in human macrophages. 2022

Y Castillo, and J E Castellanos, and G I Lafaurie, and D M Castillo
Unidad de Investigación Básica Oral (UIBO), Vicerrectoría de investigaciones, Facultad de Odontología, Universidad El Bosque, Bogotá, Colombia.

OBJECTIVE The aim was to determine the changes of inflammatory mediator expression in human macrophages stimulated with outer membrane vesicles purified from Porphyromonas gingivalis. METHODS outer membrane vesicles purified by ultracentrifugation from ATCC 33277 and W83 P. gingivalis strains were used for stimulating human macrophages and determine their inflammatory mediator expression changes. U937 monocyte cells line were differentiated into macrophages and stimulated with outer membrane vesicles for 30 min and six hours. In Independent experiments, the outer membrane vesicles and viable bacteria control were pre-treated with the gingipain inhibitors KYT-1 and KYT-36 (Arg-gingipain and Lys-gingipain, respectively) or Polymyxin-B to block the lipopolysaccharide activity to evaluate the secretion changes of immune mediators IL-1β, IL-6, TNF-α, IL-8, MCP-1, MIP-1α and RANTES by flow cytometry. A factorial ANOVA was used to analyze the data. RESULTS The outer membrane vesicles of P. gingivalis ATCC 33277 displayed higher Arg-gingipain activity than those obtained from the P. gingivalis W83 strain (0.6 U/μg vs. 0.46 U/μg). Although the outer membrane vesicles of P. gingivalis stimulated the production of cytokines and chemokines, specific Arg-gingipain and Lys-gingipain inhibition induced significant increases in IL-1β, IL-6, IL-8, MCP-1, and RANTES levels, and this induction was significantly greater at 6 h compared to 30 min (*p < 0.05). On the contrary, TNF-α secretion decreased when gingipains were blocked. CONCLUSIONS outer membrane vesicles may play a dual role during P. gingivalis infection based on their ability to induce changes in the immune responses of human macrophages, probably via gingipain-dependent events.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D003546 Cysteine Endopeptidases ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000080867 Gingipain Cysteine Endopeptidases Cysteine endoproteinases, from periodontal pathogen PORPHYROMONAS GINGIVALIS, acting as virulence factors associated with PERIODONTITIS. They are produced as pre-proproteins which mature into ARGININE and LYSINE specific endopeptidases. Arg-Gingipain,Arginine Gingipain,Gingipain,Gingipain K,Gingipain Proteases,KGP Protease,Lys-Gingipain,Lysine Gingipain,RGP-2 Gingipain,RGPB Protein,Argingipain,Gingipain R,Gingipain R1,Gingipain R2,Gingipains,Arg Gingipain,Cysteine Endopeptidases, Gingipain,Gingipain, Arginine,Gingipain, Lysine,Gingipain, RGP-2,Lys Gingipain,RGP 2 Gingipain
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015850 Interleukin-6 A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS. Hepatocyte-Stimulating Factor,Hybridoma Growth Factor,IL-6,MGI-2,Myeloid Differentiation-Inducing Protein,Plasmacytoma Growth Factor,B Cell Stimulatory Factor-2,B-Cell Differentiation Factor,B-Cell Differentiation Factor-2,B-Cell Stimulatory Factor 2,B-Cell Stimulatory Factor-2,BSF-2,Differentiation Factor, B-Cell,Differentiation Factor-2, B-Cell,IFN-beta 2,IL6,Interferon beta-2,B Cell Differentiation Factor,B Cell Differentiation Factor 2,B Cell Stimulatory Factor 2,Differentiation Factor 2, B Cell,Differentiation Factor, B Cell,Differentiation-Inducing Protein, Myeloid,Growth Factor, Hybridoma,Growth Factor, Plasmacytoma,Hepatocyte Stimulating Factor,Interferon beta 2,Interleukin 6,Myeloid Differentiation Inducing Protein,beta-2, Interferon
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016209 Interleukin-8 A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells. CXCL8 Chemokine,Chemokine CXCL8,Chemotactic Factor, Macrophage-Derived,Chemotactic Factor, Neutrophil, Monocyte-Derived,IL-8,Neutrophil-Activating Peptide, Lymphocyte-Derived,Neutrophil-Activating Peptide, Monocyte-Derived,AMCF-I,Alveolar Macrophage Chemotactic Factor-I,Anionic Neutrophil-Activating Peptide,Chemokines, CXCL8,Chemotactic Factor, Neutrophil,Granulocyte Chemotactic Peptide-Interleukin-8,IL8,Monocyte-Derived Neutrophil Chemotactic Factor,Neutrophil Activation Factor,Alveolar Macrophage Chemotactic Factor I,Anionic Neutrophil Activating Peptide,CXCL8 Chemokines,CXCL8, Chemokine,Chemokine, CXCL8,Chemotactic Factor, Macrophage Derived,Chemotactic Peptide-Interleukin-8, Granulocyte,Granulocyte Chemotactic Peptide Interleukin 8,Interleukin 8,Lymphocyte-Derived Neutrophil-Activating Peptide,Macrophage-Derived Chemotactic Factor,Monocyte-Derived Neutrophil-Activating Peptide,Neutrophil Activating Peptide, Lymphocyte Derived,Neutrophil Activating Peptide, Monocyte Derived,Neutrophil Chemotactic Factor,Neutrophil-Activating Peptide, Anionic,Peptide, Anionic Neutrophil-Activating
D016966 Porphyromonas gingivalis A species of gram-negative, anaerobic, rod-shaped bacteria originally classified within the BACTEROIDES genus. This bacterium produces a cell-bound, oxygen-sensitive collagenase and is isolated from the human mouth. Bacteroides gingivalis
D018829 Adhesins, Bacterial Cell-surface components or appendages of bacteria that facilitate adhesion (BACTERIAL ADHESION) to other cells or to inanimate surfaces. Most fimbriae (FIMBRIAE, BACTERIAL) of gram-negative bacteria function as adhesins, but in many cases it is a minor subunit protein at the tip of the fimbriae that is the actual adhesin. In gram-positive bacteria, a protein or polysaccharide surface layer serves as the specific adhesin. What is sometimes called polymeric adhesin (BIOFILMS) is distinct from protein adhesin. Adhesins, Fimbrial,Bacterial Adhesins,Fimbrial Adhesins,Adhesin, Bacterial,Bacterial Adhesin

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