Dataset Information

Synergistic enhancement of production of proinflammatory cytokines of human peripheral blood monocytes by anti-Sm and anti-RNP antibodies.

ABSTRACT: The present study was performed to elucidate the roles of serum anti-Sm antibodies in the pathogenesis of systemic lupus erythematosus (SLE). Highly purified peripheral blood monocytes obtained from healthy donors were cultured in the presence of monoclonal anti-Sm antibody (anti-Sm mAb), monoclonal anti-U1-RNP antibody (anti-RNP mAb) or control murine IgG1 or IgG3. After various periods of incubation, levels of IL-6 and TNF-? in the culture supernatants were measured by ELISA and the expression of mRNA for various molecules in monocytes was determined using RT-PCR. Flow cytometry analysis confirmed the bindings of anti-Sm mAb and anti-RNP mAb on viable human monocytes. Both anti-Sm mAb and anti-RNP mAb significantly increased the production of IL-6 and TNF-? of human monocytes in a dose-dependent manner, although the latter was more potent than the former. Of note, anti-Sm mAb synergistically enhanced the production and mRNA expression of IL-6 and TNF-? of human monocytes in the presence of anti-RNP mAb. Notably, anti-RNP mAb, but not anti-Sm mAb, significantly enhanced the mRNA expression of RelA in human monocytes. Finally, anti-Sm mAb still up-regulated the IL-6 production of monocytes in the presence of anti-RNP mAb under the influence of N-acetyl cysteine or pyrrolidine dithiocarbamate that totally abrogated the IL-6 production provoked by anti-Sm mAb alone in the absence of anti-RNP mAb. These results demonstrate that anti-Sm and anti-RNP antibodies synergistically up-regulate the expression of IL-6 and TNF-? in human monocytes. The data also suggest that the effect of anti-Sm in the synergy with anti-RNP might not involve NFkB activation.

SUBMITTER: Matsueda Y

PROVIDER: S-EPMC6301657 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Synergistic enhancement of production of proinflammatory cytokines of human peripheral blood monocytes by anti-Sm and anti-RNP antibodies.

Matsueda Yu Y Arinuma Yoshiyuki Y Nagai Tatsuo T Hirohata Shunsei S

PloS one 20181220 12

The present study was performed to elucidate the roles of serum anti-Sm antibodies in the pathogenesis of systemic lupus erythematosus (SLE). Highly purified peripheral blood monocytes obtained from healthy donors were cultured in the presence of monoclonal anti-Sm antibody (anti-Sm mAb), monoclonal anti-U1-RNP antibody (anti-RNP mAb) or control murine IgG1 or IgG3. After various periods of incubation, levels of IL-6 and TNF-α in the culture supernatants were measured by ELISA and the expression ...[more]

PMID: 30571738

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Project description:Galectin-2 is a monocyte-expressed carbohydrate-binding lectin, for which increased expression is genetically determined and associated with decreased collateral arteriogenesis in obstructive coronary artery disease patients. The inhibiting effect of galectin-2 on arteriogenesis was confirmed in vivo, but the mechanism is largely unknown. In this study we aimed to explore the effects of galectin-2 on monocyte/macrophage phenotype in vitro and vivo, and to identify the receptor by which galectin-2 exerts these effects. We now show that the binding of galectin-2 to different circulating human monocyte subsets is dependent on monocyte surface expression levels of CD14. The high affinity binding is blocked by an anti-CD14 antibody but not by carbohydrates, indicating a specific protein-protein interaction. Galectin-2 binding to human monocytes modulated their transcriptome by inducing proinflammatory cytokines and inhibiting pro-arteriogenic factors, while attenuating monocyte migration. Using specific knock-out mice, we show that galectin-2 acts through the CD14/toll-like receptor (TLR)-4 pathway. Furthermore, galectin-2 skews human macrophages to a M1-like proinflammatory phenotype, characterized by a reduced motility and expression of an anti-arteriogenic cytokine/growth factor repertoire. This is accompanied by a switch in surface protein expression to CD40-high and CD206-low (M1). In a murine model we show that galectin-2 administration, known to attenuate arteriogenesis, leads to increased numbers of CD40-positive (M1) and reduced numbers of CD206-positive (M2) macrophages surrounding actively remodeling collateral arteries. In conclusion galectin-2 is the first endogenous CD14/TLR4 ligand that induces a proinflammatory, non-arteriogenic phenotype in monocytes/macrophages. Interference with CD14-Galectin-2 interaction may provide a new intervention strategy to stimulate growth of collateral arteries in genetically compromised cardiovascular patients.

Dataset Information

Synergistic enhancement of production of proinflammatory cytokines of human peripheral blood monocytes by anti-Sm and anti-RNP antibodies.

Publications

Synergistic enhancement of production of proinflammatory cytokines of human peripheral blood monocytes by anti-Sm and anti-RNP antibodies.

Similar Datasets

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