Author:
Dawson Harry D,Collins Gary,Pyle Robert,Key Michael,Taub Dennis D
Abstract
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-γ and TNF-α 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-α (RAR-α)-selective agonist, AM580 but not with the RAR-β/γ 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-α-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-α-selective antagonist, RO 41–5253, inhibited these effects.
Conclusion
These results strongly support a role for RAR-α engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.
Publisher
Springer Science and Business Media LLC
Reference60 articles.
1. Napoli JL: Quantification of physiological levels of retinoic acid. Methods in Enzymology. 1986, 123: 112-124.
2. Kojima R, Fujimori T, Kiyota N, Toriya Y, Fukuda T, Ohashi T, Sato T, Yoshizawa Y, Takeyama K, Mani H, Masushige D, Kato S: In vivo isomerization of retinoic acids. Rapid isomer exchange and gene expression. Journal of Biological Chemistry. 1994, 269 (51): 32700-32707.
3. Kurlansky SB, Gamble MV, Ramakrishnan R, Blaner WS: Plasma delivery of retinoic acid to tissues in the rat. Journal of Biological Chemistry. 1995, 270: 17850-17857. 10.1074/jbc.270.30.17850.
4. Moise AR, Kuksa V, Blaner WS, Baehr W, Palczewski K: Metabolism and transactivation activity of 13,14-dihydroretinoic acid. J Biol Chem. 2005, 280 (30): 27815-27825. 10.1074/jbc.M503520200.
5. Ziouzenkova O, Orashanu G, Sukhova G, Lau E, Berger JP, Tang G, Krinsky NI, Dolnikowski GG, Plutzky J: Asymmetric cleavage of {beta} -carotene yields a transcriptional repressor of RXR and PPAR responses. Mol Endocrinol. 2006
Cited by
49 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献