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Modern Rheumatology
Erschienen in: Modern Rheumatology 3/2010

01.06.2010 | Original Article

The effect of synthetic retinoid, Am80, on T helper cell development and antibody production in murine collagen-induced arthritis

verfasst von: Aya Sato, Kaori Watanabe, Kayoko Kaneko, Yousuke Murakami, Miwako Ishido, Nobuyuki Miyasaka, Toshihiro Nanki

Erschienen in: Modern Rheumatology | Ausgabe 3/2010

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Abstract

Retinoids are known to promote T helper (Th)2 and regulatory T cell (Treg) differentiation, and suppress Th1 and Th17 in vitro. Am80, a synthetic retinoid, is reported to ameliorate collagen-induced arthritis (CIA). The aims of this study are to determine the effects of Am80 on CIA in detail, and on Th development and antibody (Ab) production in vivo. Murine CIA was induced by immunization with bovine type II collagen (CII) at days 1 and 22. Treatment with Am80 from day 1 to 35 significantly lowered clinical arthritis score, suppressed cellular infiltration and bone destruction in the joint, decreased interleukin (IL)-17 and increased interferon (IFN)-γ production by CII-stimulated splenocytes, and decreased proportion of Foxp3+ splenic CD4 T cells and serum anti-CII Ab levels. Thus, Am80 inhibited Th17 and Treg and enhanced Th1 differentiation in vivo. In contrast, Am80 applied from day 15 to 35 did not alter arthritis score, IL-17 or IFN-γ production by CII-stimulated splenocytes, but decreased the proportion of Foxp3+ splenic CD4 T cells and serum anti-CII Ab levels. Am80 exhibits inhibitory effects on CIA and might regulate both Th development and Ab production in vivo. Decreased Th17 by treatment with Am80 might be responsible for the attenuation of arthritis.
Literatur
1.
Hashimoto Y. Retinobenzoic acids and nuclear retinoic acid receptors. Cell Struct Funct. 1991;16:113–23.CrossRefPubMed
2.
Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996;10:940–54.PubMed
3.
Sporn MB, Roberts AB. Cervical dysplasia regression induced by all-trans-retinoic acid. J Natl Cancer Inst. 1994;86:476–7.CrossRefPubMed
4.
Beehler BC, Brinckerhoff CE, Ostrowski J. Selective retinoic acid receptor ligands for rheumatoid arthritis. Curr Opin Investig Drugs. 2004;5:1153–7.PubMed
5.
Kang BY, Chung SW, Kim SH, Kang SN, Choe YK, Kim TS. Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppresses Th1 cytokine profile in CD4+ T cells. Br J Pharmacol. 2000;130:581–6.CrossRefPubMed
6.
Kirchmeyer M, Koufany M, Sebillaud S, Netter P, Jouzeau JY, Bianchi A. All-trans retinoic acid suppresses interleukin-6 expression in interleukin-1-stimulated synovial fibroblasts by inhibition of ERK1/2 pathway independently of RAR activation. Arthritis Res Ther. 2008;10:R141.CrossRefPubMed
7.
Pino-Lagos K, Benson MJ, Noelle RJ. Retinoic acid in the immune system. Ann N Y Acad Sci. 2008;1143:170–87.CrossRefPubMed
8.
Hoag KA, Nashold FE, Goverman J, Hayes CE. Retinoic acid enhances the T helper 2 cell development that is essential for robust antibody responses through its action on antigen-presenting cells. J Nutr. 2002;132:3736–9.PubMed
9.
Iwata M, Eshima Y, Kagechika H. Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors. Int Immunol. 2003;15:1017–25.CrossRefPubMed
10.
Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic acid receptor-a favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol. 2007;37:2396–9.CrossRefPubMed
11.
Elias KM, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood. 2008;111:1013–20.CrossRefPubMed
12.
Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science. 2007;317:256–60.CrossRefPubMed
13.
Nanki T, Lipsky PE. Cytokine, activation marker, and chemokine receptor expression by individual CD4+ memory T cells in rheumatoid arthritis synovium. Arthritis Res. 2000;2:415–23.CrossRefPubMed
14.
Morita Y, Yamamura M, Kawashima M, Harada S, Tsuji K, Shibuya K, et al. Flow cytometric single-cell analysis of cytokine production by CD4+ T cells in synovial tissue and peripheral blood from patients with rheumatoid arthritis. Arthritis Rheum. 1998;41:1669–76.CrossRefPubMed
15.
Yamada H, Nakashima Y, Okazaki K, Mawatari T, Fukushi JI, Kaibara N, et al. Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:1299–304.CrossRefPubMed
16.
Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, et al. Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 1999;42:963–70.CrossRefPubMed
17.
Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, et al. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005;7:R784–95.CrossRefPubMed
18.
Tobita T, Takeshita A, Kitamura K, Ohnishi K, Yanagi M, Hiraoka A, et al. Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia relapsed from complete remission induced by all-trans retinoic acid. Blood. 1997;90:967–73.PubMed
19.
Miwako I, Kagechika H. Tamibarotene. Drugs Today (Barc). 2007;43:563–8.CrossRef
20.
Ohnishi K. PML-RARa inhibitors (ATRA, tamibaroten, arsenic troxide) for acute promyelocytic leukemia. Int J Clin Oncol. 2007;12:313–7.CrossRefPubMed
21.
Kuwabara K, Shudo K, Hori Y. Novel synthetic retinoic acid inhibits rat collagen arthritis and differentially affects serum immunoglobulin subclass levels. FEBS Lett. 1996;378:153–6.CrossRefPubMed
22.
Takeda N, Manabe I, Shindo T, Iwata H, Iimuro S, Kagechika H, et al. Synthetic retinoid Am80 reduces scavenger receptor expression and atherosclerosis in mice by inhibiting IL-6. Arterioscler Thromb Vasc Biol. 2006;26:1177–83.CrossRefPubMed
23.
Kagechika H. Novel synthetic retinoids and separation of the pleiotropic retinoidal activities. Curr Med Chem. 2002;9:591–608.CrossRefPubMed
24.
Ohyanagi N, Ishido M, Suzuki F, Kaneko K, Kubota T, Miyasaka N, et al. Retinoid ameliorates experimental autoimmune myositis, with modulation of Th cell differentiation and antibody production in vivo. Arthritis Rheum. 2009;60:3118–27.CrossRefPubMed
25.
Klemann C, Raveney BJ, Klemann AK, Ozawa T, von Horsten S, Shudo K, et al. Synthetic retinoid AM80 inhibits Th17 cells and ameliorates experimental autoimmune encephalomyelitis. Am J Pathol. 2009;174(6):2234–45.CrossRefPubMed
26.
Nagai H, Matsuura S, Bouda K, Takaoka Y, Wang T, Niwa S, et al. Effect of Am-80, a synthetic derivative of retinoid, on experimental arthritis in mice. Pharmacology. 1999;58:101–12.CrossRefPubMed
27.
Wakamatsu K, Nanki T, Miyasaka N, Umezawa K, Kubota T. Effect of a small molecule inhibitor of nuclear factor-κB nuclear translocation in a murine model of arthritis and cultured human synovial cells. Arthritis Res Ther. 2005;7:R1348–59.CrossRefPubMed
28.
Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, et al. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. 2004;50:650–9.CrossRefPubMed
29.
Bush KA, Farmer KM, Walker JS, Kirkham BW. Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 2002;46:802–5.CrossRefPubMed
30.
Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171:6173–7.PubMed
31.
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32.CrossRefPubMed
32.
Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.CrossRefPubMed
33.
Manoury-Schwartz B, Chiocchia G, Bessis N, Abehsira-Amar O, Batteux F, Muller S, et al. High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. J Immunol. 1997;158:5501–6.PubMed
34.
Vermeire K, Heremans H, Vandeputte M, Huang S, Billiau A, Matthys P. Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice. J Immunol. 1997;158:5507–13.PubMed
35.
Sarkar S, Cooney LA, White P, Dunlop DB, Endres J, Jorns JM, et al. Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4. Arthritis Res Ther. 2009;11:R158.CrossRefPubMed
36.
Mohty M, Morbelli S, Isnardon D, Sainty D, Arnoulet C, Gaugler B, et al. All-trans retinoic acid skews monocyte differentiation into interleukin-12-secreting dendritic-like cells. Br J Haematol. 2003;122:829–36.CrossRefPubMed
37.
Wei J, Duramad O, Perng OA, Reiner SL, Liu YJ, Qin FX. Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3+ regulatory T cells. Proc Natl Acad Sci USA. 2007;104:18169–74.CrossRefPubMed
38.
Wang Z, Hong J, Sun W, Xu G, Li N, Chen X, et al. Role of IFN-gamma in induction of Foxp3 and conversion of CD4+CD25− T cells to CD4+ Tregs. J Clin Invest. 2006;116:2434–41.PubMed
39.
Nozaki Y, Yamagata T, Sugiyama M, Ikoma S, Kinoshita K, Funauchi M. Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis. Clin Immunol. 2006;119:272–9.CrossRefPubMed
40.
Tokuyama H, Tokuyama Y. The regulatory effects of all-trans-retinoic acid on isotype switching: retinoic acid induces IgA switch rearrangement in cooperation with IL-5 and inhibits IgG1 switching. Cell Immunol. 1999;192:41–7.CrossRefPubMed
41.
Takagi N, Mihara M, Moriya Y, Nishimoto N, Yoshizaki K, Kishimoto T, et al. Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis. Arthritis Rheum. 1998;41:2117–21.CrossRefPubMed
42.
Fujimoto M, Serada S, Mihara M, Uchiyama Y, Yoshida H, Koike N, et al. Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses. Arthritis Rheum. 2008;58:3710–9.CrossRefPubMed
43.
Nagpal S, Cai J, Zheng T, Patel S, Masood R, Lin GY, et al. Retinoid antagonism of NF-IL6: insight into the mechanism of antiproliferative effects of retinoids in Kaposi’s sarcoma. Mol Cell Biol. 1997;17:4159–68.PubMed
Metadaten
Titel
The effect of synthetic retinoid, Am80, on T helper cell development and antibody production in murine collagen-induced arthritis
verfasst von
Aya Sato
Kaori Watanabe
Kayoko Kaneko
Yousuke Murakami
Miwako Ishido
Nobuyuki Miyasaka
Toshihiro Nanki
Publikationsdatum
01.06.2010
Verlag
Springer Japan
Erschienen in
Modern Rheumatology / Ausgabe 3/2010
Print ISSN: 1439-7595
Elektronische ISSN: 1439-7609
DOI
https://doi.org/10.1007/s10165-009-0265-y

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