Limits...
The Retinoic Acid Receptor-alpha mediates human T-cell activation and Th2 cytokine and chemokine production.

Dawson HD, Collins G, Pyle R, Key M, Taub DD - BMC Immunol. (2008)

Bottom Line: Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA), and the retinoic acid receptor-alpha (RAR-alpha)-selective agonist, AM580 but not with the RAR-beta/gamma ligand, 4-hydroxyphenylretinamide (4-HPR).The RAR-alpha-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-alpha-selective antagonist, RO 41-5253, inhibited these effects.These results strongly support a role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA. harry.dawson@ars.usda.gov

ABSTRACT

Background: We have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-gamma and TNF-alpha expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA), and the retinoic acid receptor-alpha (RAR-alpha)-selective agonist, AM580 but not with the RAR-beta/gamma ligand, 4-hydroxyphenylretinamide (4-HPR).

Results: The increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-alpha-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-alpha-selective antagonist, RO 41-5253, inhibited these effects.

Conclusion: These results strongly support a role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

Show MeSH

Related in: MedlinePlus

A RAR- α agonist induces and the RAR- α antagonist, R0 41–5254, reduces the expression of CD69 and CD38 on human T cells during activation. PBMC were activated with anti-CD3, mAb in the presence or absence of control ETOH or 10-7 M of ATRA, AM580, or RO41-5254 for 48 h. After activation, the cells were harvested and the cell surface levels of CD69 and CD38 were assessed by flow cytometric analysis as described in the Materials and Methods. The data are representative of all of the donors tested.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2394516&req=5

Figure 7: A RAR- α agonist induces and the RAR- α antagonist, R0 41–5254, reduces the expression of CD69 and CD38 on human T cells during activation. PBMC were activated with anti-CD3, mAb in the presence or absence of control ETOH or 10-7 M of ATRA, AM580, or RO41-5254 for 48 h. After activation, the cells were harvested and the cell surface levels of CD69 and CD38 were assessed by flow cytometric analysis as described in the Materials and Methods. The data are representative of all of the donors tested.

Mentions: Similar to the data on ATRA and 9-cis-RA shown in Table 3, AM580 increased the MCN and the percentage of T cells expressing CD69 (Figure 7A) and CD38 (Figure 7B) in anti-CD3, activated PBMC cultures. We typically observed a 2–3 fold increase in the MCN of CD69 and CD38 using these retinoids. Conversely, the RAR-α-selective antagonist inhibited the expression of these molecules (Figure 7A and 7B). Thus, it would appear that ATRA and the RAR-α selective retinoid, AM580, induce similar and comparable activation of human T cells in our culture system. In addition, we have also examined the comparative ability of the RAR-γ agonist SR11254 and RAR-β/γ(agonist, Ro 44–5743, to stimulate CD38 and CD69 expression in anti-CD3,- or anti-CD3/anti-CD28-stimulated PBMC and T cells. Compared to ATRA and AM580, these agonists were significantly less effective at inducing the expression of CD38 and CD69 (data not shown).


The Retinoic Acid Receptor-alpha mediates human T-cell activation and Th2 cytokine and chemokine production.

Dawson HD, Collins G, Pyle R, Key M, Taub DD - BMC Immunol. (2008)

A RAR- α agonist induces and the RAR- α antagonist, R0 41–5254, reduces the expression of CD69 and CD38 on human T cells during activation. PBMC were activated with anti-CD3, mAb in the presence or absence of control ETOH or 10-7 M of ATRA, AM580, or RO41-5254 for 48 h. After activation, the cells were harvested and the cell surface levels of CD69 and CD38 were assessed by flow cytometric analysis as described in the Materials and Methods. The data are representative of all of the donors tested.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2394516&req=5

Figure 7: A RAR- α agonist induces and the RAR- α antagonist, R0 41–5254, reduces the expression of CD69 and CD38 on human T cells during activation. PBMC were activated with anti-CD3, mAb in the presence or absence of control ETOH or 10-7 M of ATRA, AM580, or RO41-5254 for 48 h. After activation, the cells were harvested and the cell surface levels of CD69 and CD38 were assessed by flow cytometric analysis as described in the Materials and Methods. The data are representative of all of the donors tested.
Mentions: Similar to the data on ATRA and 9-cis-RA shown in Table 3, AM580 increased the MCN and the percentage of T cells expressing CD69 (Figure 7A) and CD38 (Figure 7B) in anti-CD3, activated PBMC cultures. We typically observed a 2–3 fold increase in the MCN of CD69 and CD38 using these retinoids. Conversely, the RAR-α-selective antagonist inhibited the expression of these molecules (Figure 7A and 7B). Thus, it would appear that ATRA and the RAR-α selective retinoid, AM580, induce similar and comparable activation of human T cells in our culture system. In addition, we have also examined the comparative ability of the RAR-γ agonist SR11254 and RAR-β/γ(agonist, Ro 44–5743, to stimulate CD38 and CD69 expression in anti-CD3,- or anti-CD3/anti-CD28-stimulated PBMC and T cells. Compared to ATRA and AM580, these agonists were significantly less effective at inducing the expression of CD38 and CD69 (data not shown).

Bottom Line: Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA), and the retinoic acid receptor-alpha (RAR-alpha)-selective agonist, AM580 but not with the RAR-beta/gamma ligand, 4-hydroxyphenylretinamide (4-HPR).The RAR-alpha-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-alpha-selective antagonist, RO 41-5253, inhibited these effects.These results strongly support a role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA. harry.dawson@ars.usda.gov

ABSTRACT

Background: We have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-gamma and TNF-alpha expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA), and the retinoic acid receptor-alpha (RAR-alpha)-selective agonist, AM580 but not with the RAR-beta/gamma ligand, 4-hydroxyphenylretinamide (4-HPR).

Results: The increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-alpha-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-alpha-selective antagonist, RO 41-5253, inhibited these effects.

Conclusion: These results strongly support a role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

Show MeSH
Related in: MedlinePlus