Journal of Clinical Immunology

, Volume 27, Issue 2, pp 193–200

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

Article

DOI: 10.1007/s10875-006-9068-5

Cite this article as:
Wang, X., Allen, C. & Ballow, M. J Clin Immunol (2007) 27: 193. doi:10.1007/s10875-006-9068-5

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.

KEY WORDS:

Retinoic acid monocytes/macrophages cord blood mononuclear cells cytokines IL-10 TNF-α; IL-12 

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

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Children’s HospitalMedical Center of Fudan UniversityShanghaiP.R. China
  2. 2.Division of Allergy/Clinical Immunology and Pediatric RheumatologyDepartment of Pediatrics, Women’s and Children’s Hospital of Buffalo, SUNY Buffalo School of Medicine and Biomedical SciencesBuffaloUSA
  3. 3.Division of Allergy/Clinical Immunology and Pediatric RheumatologyDepartment of Pediatrics, Women’s and Children’s Hospital of Buffalo, SUNY Buffalo School of Medicine and Biomedical SciencesBuffaloUSA

Personalised recommendations