Tryptanthrin inhibits Th2 development, and IgE-mediated degranulation and IL-4 production by rat basophilic leukemia RBL-2H3 cells

• Published in: Journal of ethnopharmacology Vol. 134; no. 2; pp. 450 - 459
• Main Authors: Iwaki, Kanso, Ohashi, Emiko, Arai, Norie, Kohno, Keizo, Ushio, Shimpei, Taniguchi, Makoto, Fukuda, Shigeharu
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 24.03.2011; Elsevier
• Subjects: Animals; Anti-Allergic Agents - pharmacology; Anti-Allergic Agents - therapeutic use; Antigens, Plant; Basophils - drug effects; Basophils - physiology; Biological and medical sciences; Cell Degranulation - drug effects; Cell Differentiation - drug effects; Cell Line, Tumor; Degranulation; Down-Regulation; Female; General pharmacology; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Immunoglobulin E - metabolism; Interleukin-4 (IL-4); Interleukin-4 - biosynthesis; Leukemia, Basophilic, Acute; Mast Cells; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phosphorylation; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Polygonum - chemistry; Proto-Oncogene Proteins c-maf - genetics; Proto-Oncogene Proteins c-maf - metabolism; Quinazolines - pharmacology; Quinazolines - therapeutic use; Rats; RBL-2H3 cells; RNA, Messenger - metabolism; Signal Transduction; T helper type 2 (Th2) cells; Th2 Cells - drug effects; Th2 Cells - physiology; Tryptanthrin; Type I allergy; Degranulation; Tryptanthrin; Type I allergy; Interleukin-4 (IL-4); T helper type 2 (Th2) cells; RBL-2H3 cells; Allergy; Rat; IgE; Granulocyte; Medicinal plant; Myeloproliferative syndrome; Alkaloid; Interleukin 4; T-Lymphocyte; Th2 lymphocyte; Tumor cell; Immunopathology; Basophilic leukemia; Pharmacognosy; Cytokine; Rodentia; Malignant hemopathy; In vitro; Vertebrata; Mammalia; Animal; Plant origin; Cancer
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2010.12.041

Results of our study suggest that Tryptanthrin effectively inhibits the effector and exacerbation responses, as well as the initiating responses, of Type I allergy. Tryptanthrin is a compound isolated from Polygonum tinctorium, which is a known folk medicine with various biological activities. Allergic diseases are initiated by the development of allergen-specific T helper type 2 (Th2) cells and amplified by the degranulation of and cytokine release from basophils and mast cells during an effector phase. We found that Tryptanthrin could down-regulate IL-4 production by Th2 cells, while IFN-γ production by Th1 cells was not affected. Since IL-4 produced by basophils and effector Th2 cells has been shown to play important roles in the development and amplification of Th2-dominated allergic responses, we examined the effects of Tryptanthrin on the initiation and effector phase responses of Type I allergy in vitro. To determine the mechanisms of Tryptanthrin-induced down-regulation of IL-4 production, the expression of Th2-specific transcription factors, c-Maf and GATA-3, was analyzed by RT-PCR. The effects of Tryptanthrin on Th cell differentiation were evaluated using CD4+ T cells purified from spleen cells of Sugi basic protein (SBP)-immunized BALB/c mice. In primary cultures, cells were stimulated with SBP and antigen-presenting cells under neutral or Th2-skewing conditions in the presence or absence of Tryptanthrin. Cytokines produced by differentiated Th cells in secondary cultures were analyzed by ELISA. The effects of Tryptanthrin on IgE-mediated degranulation and IL-4 production were determined using rat basophilic leukemia (RBL-2H3) cells. Phosphorylation of ERK1/2 and Akt in Tryptanthrin-treated RBL-2H3 cells was analyzed to determine the mechanism of Tryptanthrin actions. Tryptanthrin suppressed c-Maf mRNA expression in Th2 clone cells, and even under Th2-skewing conditions, Tryptanthrin inhibited differentiation toward the Th2 phenotype, which is an essential event for the initiation phase of allergic diseases. Tryptanthrin also inhibited the IgE-mediated degranulation of and IL-4 production by RBL-2H3 cells, probably due to inhibiting IgE-mediated signaling pathways, including the phosphorylation of ERK1/2 and Akt. These findings suggest that Tryptanthrin effectively inhibits the effector and exacerbation responses, as well as the initiator responses, of Type I allergy. Thus, Tryptanthrin may have beneficial effects for immediate-type allergic responses.