Suppression of IgE Production by IPD-1151T (Suplatast Tosilate), a New Dimethylsulfonium Agent: (1) Regulation of Murine IgE Response

Yanagihara,; Yukiyoshi,; Kiniwa,; Mamoru,; Ikizawa,; Koichi,; Yamaya,; Hidetoshi,; Shida,; Takao,; Matsuura,; Naosuke,; Koda,; Akihide,

doi:10.1254/jjp.61.23

Cited by 54 publications

(46 citation statements)

References 25 publications

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“…A Th2 inhibitor, suplatast tosilate, was reported to inhibit IL-4 production from mouse D10G4.1 cells at 10 to 100 M (Yanagihara et al, 1993); however, we did not observe obvious effect up to 100 M in IL-4 production from mouse splenic B cells, whereas the inhibition was apparent at 1000 M in human PBMCs in our experiment. This indicates that the activity of suplatast tosilate is not powerful in primary cells under our experimental conditions.…”

Section: Discussioncontrasting

confidence: 96%

JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model

Mimura¹,

Shinozaki²,

Kawasaki³

et al. 2005

J Pharmacol Exp Ther

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We report a novel synthetic compound JTP-27536 [(ϩ)-1,3-dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-cyclohexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate monohydrate] as an inhibitor of immunoglobulins (Igs) and interleukin (IL)-5 production in vitro and in vivo. JTP-27536 inhibited IgE production in mouse and human B cells with IC 50 values of 2.5 and 2.1 M, respectively, and the inhibition was stronger than that on IgG1 and IgM production (IC 50 Ͼ 10 M). JTP-27536 also inhibited IL-5 production in mouse splenocytes and human peripheral blood mononuclear cells with IC 50 values of 3.3 and 1.3 M, respectively, without affecting mouse interferon (IFN)-␥, IL-2, IL-4, IL-10, or human IL-4 production. In contrast, prednisolone not only inhibited mouse IgE production but also mouse IFN-␥, IL-2, IL-4, and IL-10 and human IL-4 and IL-5 production in vitro. The effect of suplatast tosilate, a Th2 cytokine inhibitor, on antibody and cytokine production was less potent than that of JTP-27536. In vivo animal experiments using dinitrophenylated ascarissensitized mice and 2,4,6-trinitro-1-chrolobenzene-induced chronic dermatitis mice showed that JTP-27536 was more potent than suplatast tosilate and comparable with prednisolone in inhibiting ear swelling, antigen-specific IgE and IL-5 production, and cell infiltrations into the inflamed tissue. These results indicate that JTP-27536 is an inhibitor of Igs, in particular IgE, and of IL-5, which has antiallergic properties in mouse dermatitis model, and suggest that an inhibitor of Igs and IL-5 like JTP-27536 may be useful as a drug for the treatment of allergic diseases.

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Section: Discussioncontrasting

confidence: 96%

JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model

Mimura¹,

Shinozaki²,

Kawasaki³

et al. 2005

J Pharmacol Exp Ther

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“…15) Our present study showed that Wistar rats exhibit a peak IgE level 10 d after sensitization using DNP-As as antigen and B. pertussis as adjuvant and produce a high level of IgE, as frequently observed in allergic disease. Consequently, female Wistar rats are suggested to be useful as a control animal group in the evaluation of such compounds as suplatast tosilate (IPD-1151T) 9,[16][17][18][19] that suppress IgE formation and Th2-type cytokines. Thus our results indicate that animal strain affects experimental results even when the identical method of disease model preparation is used.…”

Section: Discussionmentioning

confidence: 99%

Wistar Strain Rats as the Model for IgE Antibody Experiments.

Hirano

Kawasaki

Miyataka

et al. 2001

Biological & Pharmaceutical Bulletin

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In recent years, an increase has been reported globally in the number of cases of allergic disease. Japan is no exception, and allergic diseases including cedar pollenosis, atopic diseases, and extrinsic asthma have raised grave social concern.2) These allergic symptoms are generally classified as the type I allergy and well-known immediate-type reactions. They are also known to be caused by the release of mediator from target cells such as mast cells and basophils following exposure to an antigen. When an antigen enters the body, it is phagocytosed by macrophages, which then present it to T cells. Differentiated (proliferated) T cells present the antigen to B cells. After differentiation to antibody-forming cells by the action of cytokines such as interleukin (IL)-4, B cells produce IgE antibody.3) An increase in plasma IgE level is observed in about 80% of patients with atopic dermatitis and this is closely related to their long-term serious symptoms. 4,5) We attempted to prepare rats with high IgE as a model of patients with allergic diseases. Rats were activated using 2,4-dinitrophenylated ascaris extract (DNP-As) as antigen and were immunized with killed Bordetella pertussis as adjuvant, which is reported to enhance IgE antibody formation in rats and mice. [6][7][8] The amount of IgE antibody formed and its change over time were then studied in the rats. MATERIALS AND METHODSAnimals Six-week-old male and female, Sprague-Dawley (SD), Donryu, and Wistar strain rats were kindly supplied by Japan SLC Inc. The animals were used in the experiments after preliminary feeding for one week.Reagents DNP-As and killed B. pertussis were purchased from LSL Co., Ltd., and Chiba Serum Research Laboratory, respectively. Morinaga Institute of Biological Sciences kindly donated enzyme-linked immunosorbent assay (ELISA) kits (Morinaga Rat IgE ELISA Kit).Immunization Immunization of rats was performed with reference to the method of Matsuura et al.9) DNP-As (1 mg per animal) was dissolved in physiological saline 0.1 ml and the solution was mixed with killed B. pertussis 0.5 ml of containing 10 10 cells. The mixture was subcutaneously injected in the paws of each rat for early immunization. Five days after early immunization, a solution of DNPAs 0.5 mg in physiological saline 0.25 ml was injected into the back muscle of each rat to produce additional immunization.Blood Sampling and Measurement Blood was drawn from the jugular vein of each rat 0, 5, 10, 20, and 25 d after additional immunization. The day of additional immunization was taken as day 0. The blood was centrifuged at 4°C for 10 min at 700ϫg and the plasma obtained was used as the sample. The plasma was frozen at Ϫ20°C and stored until the time of IgE determination. The amount of IgE was determined by the EIA sandwich method using ELISA. The sample was placed in a plate coated with solid phase-bound anti-rat IgE monoclonal antibody and the plate was allowed to stand at room temperature for 4 h, during which the antibody formed a complex with rat IgE. After washing each...

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“…This drug decreased the levels of some immune system associated substances such as Interleukin-4 (IL-4), eosinophils, and Immunoglobulin E (IgE) [2]. Because type I allergic reactions are caused by IgE, a drug that can specifically inhibit IgE antibody formation, is expected to be efficacious for the fundamental treatment of type I allergic diseases.…”

Section: Introductionmentioning

confidence: 99%

Lead Generation of Anti-allergic Agent ; Suplatast Tosilate

Tada

Yamawaki

Ueda

et al. 2001

CBIJ

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The reaction of transmethylation plays an important role in the immune system. Some kinds of sulfonium compounds, which have a labile methyl group, are considered to become the supply source for methyl groups in biological systems. We examined the physicochemical properties of sulfonium compounds from the point of structure activity relationships analysis in order to develop an antiallergy drug. We found that several sulfonium compounds have immunological activity, and 2-hydroxyethyldimethylsulfonium p-toluenesulfonate (4) was chosen as the lead compound for further studies.

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Suppression of IgE Production by IPD-1151T (Suplatast Tosilate), a New Dimethylsulfonium Agent: (1) Regulation of Murine IgE Response

Cited by 54 publications

References 25 publications

JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model

JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model

Wistar Strain Rats as the Model for IgE Antibody Experiments.

Lead Generation of Anti-allergic Agent ; Suplatast Tosilate

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