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Retinoic Acid Enhances the Production of IL-10 While Reducing the Synthesis of IL-12 and TNF-α from LPS-Stimulated Monocytes/Macrophages

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Vitamin A and its metabolites, e.g., all trans-retinoic acid (atRA) and 9-cis-retinoic acid have attracted considerable attention as compounds that have a broad range of immune modulating effects on both humoral and cellular immune responses. The cellular and molecular mechanisms that underlie the effects of retinoids on the immune system remain to be more clearly defined. These immune modulating effects of atRA may be mediated by cytokines elaborated by monocytes and other cell types. To further understand the mechanism(s) by which retinoids affect the immune response, we examined the effects of atRA on several proinflammatory and immune modulating cytokines produced by monocytes. The effects of atRA on LPS-induced mRNA expression of IL-10, IL-12p40, TNF-α, IL-18, and TGF-β in the THP-1 monocyte/macrophage cell line and in cord blood mononuclear cells were measured by competitive RT-PCR. The ELISPOT was employed to evaluate IL-10 and TNF-α protein production enumerating the number of IL-10 and TNF-α producing cells. The addition of atRA to cell cultures potentiated the LPS-induced IL-10 mRNA expression and the number of IL-10 secreting cells from THP-1 cells and cord blood mononuclear cells. In contrast, the addition of atRA inhibited the LPS-induced TNF-α and IL-12p40 mRNA expression, and the number of ELISPOT positive cells for TNF-α. atRA did not change the LPS-induced mRNA expression of IL-18 and TGF-β. These results suggest that atRA may have multiple effects on LPS-induced monocyte/macrophage derived cytokines. While atRA downregulated the proinflammatory cytokines, e.g., IL-12 and TNF-α, the production of an immune modulating cytokine, IL-10 was enhanced by atRA. The effects of atRA on these cytokines may play an important role in the modulation of the immune and inflammatory responses.

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Abbreviations

CBMC:

cord blood mononuclear cells

atRA:

all-trans retinoic acid

RT-PCR:

reverse transcriptase-polymerase chain reaction

IL:

interleukin

TNF:

tumor necrosis factor

LPS:

lipopolysaccharide

ELISPOT:

enzyme-linked immunosorbent spot

DMSO:

dimethyl sulfoxide

PHA:

phytohemagglutinin

SAC:

Staphylococcus aureus Cowans strain

G3PDH:

Glyceraldehyde 3-phosphate dehydrogenase

Ig:

immunoglobulin

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ACKNOWLEDGMENTS

The authors wish to thank Drs. Abdul Qadir Haseeb and Jennifer Pendleton for their help in this study. This work was supported in part by NIH Grant NICHD R01-HD37263.

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Authors and Affiliations

  1. Children’s Hospital, Medical Center of Fudan University, Shanghai, P.R. China

    Xiaochuan Wang

  2. Division of Allergy/Clinical Immunology and Pediatric Rheumatology, Department of Pediatrics, Women’s and Children’s Hospital of Buffalo, SUNY Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA

    Cheryl Allen & Mark Ballow

  3. Division of Allergy/Clinical Immunology and Pediatric Rheumatology, Department of Pediatrics, Women’s and Children’s Hospital of Buffalo, SUNY Buffalo School of Medicine and Biomedical Sciences, 219 Bryant Street, Buffalo, New York, 14222, USA

    Mark Ballow

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  1. Xiaochuan Wang
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Correspondence to Mark Ballow.

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Wang, X., Allen, C. & Ballow, M. Retinoic Acid Enhances the Production of IL-10 While Reducing the Synthesis of IL-12 and TNF-α from LPS-Stimulated Monocytes/Macrophages. J Clin Immunol 27, 193–200 (2007). https://doi.org/10.1007/s10875-006-9068-5

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