Effect of Am-80, a Retinoid Derivative, on 2,4-Dinitrofluorobenzene-Induced Contact Dermatitis in Mice

Niwa, Shin‐Ichi; Ochi, Takashi; Hirano, Yuki; Wang, Ting; Inagaki, Nobuya; Shudo, Koichi; Nagai, Hiroichi

doi:10.1159/000028371

Cited by 16 publications

(16 citation statements)

References 21 publications

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“…on September 11, 2016. by guest www.bloodjournal.org From induced contact dermatitis, 22 and atherosclerosis. 23 Because retinoids can down-regulate Th1 and Th17 cells and can ameliorate autoimmune diseases, we hypothesized that these retinoids would attenuate cGVHD.…”

Section: Discussionmentioning

confidence: 99%

“…28 Am80, a novel RAR␣/␤-specific synthetic retinoid, has a biologic activity ϳ 10 times more potent than that of ATRA 20 and directly inhibits Th1 cytokine production. 20,22,29 Therefore, we hypothesized that ATRA or Am80 downregulates both Th1 and Th17 differentiation in donor T cells, resulting in attenuation of cGVHD. To clarify whether retinoids directly inhibit the production of cytokines, PLNs were isolated from mice 14 days after allogeneic BMT and cultured with Am80 for 24 hours to determine cytokine production.…”

Section: Am80 Inhibits Donor Th1 and Th17 Cells Both In Vitro And In mentioning

confidence: 99%

“…20 Am80 also inhibits IL-6 signaling 20,21 and reduces the severity and progression of inflammatory disease models. [20][21][22][23] In the present study, we used the B10.D2 (H-2 d ) into BALB/c (H-2 d ) MHC-compatible, multiple minor histocompatibility Ag (miHA)-incompatible model of cGVHD to address the contribution of Th1/Th17 cells and the effects of retinoids on cGVHD with the use of IFN-␥ Ϫ/Ϫ mice and IL-17 Ϫ/Ϫ mice as donors. We also tested the hypothesis that the administration of Am80 ameliorates cGVHD by reducing the levels of Th1 and Th17 inflammatory cytokines and the fibrosis factor TGF-␤.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17

Nishimori

Maeda

Teshima

et al. 2012

Blood

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Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-γ-deficient and IL-17-deficient mice as donors. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-β expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD.

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Section: Discussionmentioning

confidence: 99%

Section: Am80 Inhibits Donor Th1 and Th17 Cells Both In Vitro And In mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17

Nishimori

Maeda

Teshima

et al. 2012

Blood

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“…Am80 has been reported to inhibit the development of collagen-induced arthritis in mice and rats, experimental autoimmune encephalomyelitis in rats and 2,4-dinitrofluorobenzene-induced contact dermatitis in mice. [9][10][11][12] In this study we examined the effect of Am80 administration on the development of type 1 diabetes in NOD mice in order to clarify its immunomodulatory competence.…”

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confidence: 99%

Oral Administration of Synthetic Retinoid Am80 Inhibits the Development of Type 1 Diabetes in Non-obese Diabetic (NOD) Mice

Ishido

Shudo

2009

Biological & Pharmaceutical Bulletin

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Synthetic retinoid Am80 is a potent modulator of the immune system. Am80 is effective in various experimentally induced autoimmune disorders. The purpose of this study is to confirm its effect on non-obese diabetic (NOD) mice, which spontaneously develop autoimmune type 1 diabetes. Am80 was orally administered in feed to 6 NOD mice per group at a dose of 0 (control), 0.1 (low) or 1 (high) mg/kg/d for 19 weeks. During the experiment period, the high urine glucose levels were observed in 33% mice of the control and low Am80 groups, whereas any mouse in the high Am80 group did not show abnormal urine glucose level. Histological examination showed that the average score of insulitis severity in the low Am80 group was similar to that in the control; however in the high Am80 group, the score was significantly reduced compared to that in the control group. Similarly, the severity of lymphocyte infiltration in the submandibular glands showed a tendency to decrease in the high Am80 group, but not in the low Am80 group, compared to the control. These data strongly suggest that the development of type 1 diabetes in NOD mice can be inhibited by oral administration of Am80.Key words retinoid; Am80; non-obese diabetic mouse; type 1 diabetes Type 1 diabetes is a T-cell-mediated, inflammatory autoimmune disease characterized by the infiltrate of activated T lymphocytes into the islets of Langerhans of the pancreas (insulitis), resulting in the inflammation and progressive destruction of the insulin-producing beta cells. Several factors have been proposed to be involved in the inflammatory response leading to beta cell destruction, including cytolytic lymphocytes and proinflammatory cytokines, as well as the local generation of chemokines and cellular adhesion molecules.1) The non-obese diabetic (NOD) mouse is one of the commonly used animal models of spontaneous type 1 diabetes.2) Development of type 1 diabetes in NOD mice is preceded by infiltration of pancreatic islets by mononuclear cells, and then antigen-dependent expansion of pathogenic autoreactive T-cells is observed followed by beta cell destruction and diabetes.Retinoids, analogs of vitamin A, interact with retinoic acid receptors (RARs) and/or retinoid X receptors (RXRs), and modulate the immune systems by a variety of methods including modulation of Th1/Th2 development and production of cytokines by inflammatory cells such as macrophages. Several selective RAR ligands have been reported to be effective on collagen-induced arthritis in rodents 3)

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“…8 Am80 is also known to inhibit the IL-6 signaling. 9 -11 Am80 suppresses IL-6 production in splenic mononuclear cells and reduces the severity and progression of inflammatory disease models, including 2,4-dinitrofluorobenzene-induced contact dermatitis, 10 collageninduced arthritis, 11 and allergic encephalomyelitis. 9 Recently, we reported that Am80 inhibits neointima formation in a mouse vascular injury model, suggesting it also modulates inflammatory and remodeling processes in the vessel wall.…”

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confidence: 99%

Synthetic Retinoid Am80 Reduces Scavenger Receptor Expression and Atherosclerosis in Mice by Inhibiting IL-6

Takeda

Manabe

Shindo

et al. 2006

ATVB

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Background-Macrophage scavenger receptors facilitate the uptake of modified low-density lipoprotein (LDL), formation of foam cells, and development of atherosclerosis. Given that proinflammatory cytokines, including IL-6, can modulate the macrophage foaming process, the aim of the present study was to determine whether the synthetic retinoic acid receptor-␣/␤-specific agonist Am80, which is also an IL-6 inhibitor, can modulate macrophage lipid accumulation and foam cell formation. Methods and Results-Am80 suppressed IL-6 production induced by 12-myristate 13-acetate (PMA) or angiotensin II in mouse Raw264 macrophages. It also suppressed expression of the 2 major scavenger receptors (scavenger receptor-A [SR-A] and CD36), in part by inhibiting IL-6, and inhibited macrophage foam cell formation. Systemic administration of Am80 led to reductions in the areas of atherosclerotic lesions and foam cell accumulation in the aortas of apolipoprotein E (apoE)-deficient mice and reduced serum concentrations of IL-6 and IL-1␤ without affecting body weights, serum lipid profiles or IL-10 levels. Conclusions-Am80 suppresses scavenger receptor expression and macrophage foam cell formation in vitro and prevents atherogenesis in apoE-deficient mice in vivo. This suggests Am80 is a novel candidate agent that could be highly useful in the prevention and treatment of atherosclerosis.

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Effect of Am-80, a Retinoid Derivative, on 2,4-Dinitrofluorobenzene-Induced Contact Dermatitis in Mice

Cited by 16 publications

References 21 publications

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17

Oral Administration of Synthetic Retinoid Am80 Inhibits the Development of Type 1 Diabetes in Non-obese Diabetic (NOD) Mice

Synthetic Retinoid Am80 Reduces Scavenger Receptor Expression and Atherosclerosis in Mice by Inhibiting IL-6

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