Rehmannia Glutinosa Pharmacopuncture Solution Regulates Functional Activation, FcεRI Expression, and Signaling Events in Mast Cells
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Objectives: Rehmannia glutinosa pharmacopuncture solution (RGPS) was investigated to determine both its anti-allergic inflammatory effects on mast cells and its detailed mechanism of actions. Methods: We investigated whether RGPS suppress cytokines, enzymes, FcεRI expression and FcεRI–mediated signaling in RBL-2H3 cells stimulated with anti-DNP IgE/DNP-HSA. The suppressive effects of RGPS on the levels of cytokines such as IL-1β, IL-6 and GM-CSF were measured using emzyme-linked immunospecific assay (ELISA). The mRNA expression levels of cytokines, enzymes (HDC2, COX-1, COX-2 and 5LO) and FcεRI αβγ subunits were measured using reverse transcription polymerase chain reaction (RT-PCR) method. The activation of FcεRI-mediated signaling was examined using Western blot analyses. Results: RGPS suppressed production of pro-inflammatory cytokines (IL-1β, IL-6, and GM-CSF) in stimulated RBL-2H3 cells significantly (p < 0.05). RGPS also suppressed mRNA expression of inflammatory enzymes (HDC2, COX-1, COX-2, 5LO). In addition, mRNA expression levels of FcεRIα, FcεRIβ and FcεRIγ were lowered by treatment with RGPS. Finally, RGPS prevented phosphrylation of Lyn, Syk, LAT, Gab2, PLCγ1/2, PI3K, Akt, cPLA2 and IκBα. Conclusion: RGPS effectively suppresses mast cell activations such as degranulation and inflammatory response via down-regulation of the FcεRI-mediated signaling pathways in IgE/Ag-stimulated mast cells.
Abstract
Objectives: Rehmannia glutinosa pharmacopuncture solution (RGPS) was investigated to determine both its anti-allergic inflammatory effects on mast cells and its detailed mechanism of actions. Methods: We investigated whether RGPS suppress cytokines, enzymes, FcεRI expression and FcεRI–mediated signaling in RBL-2H3 cells stimulated with anti-DNP IgE/DNP-HSA. The suppressive effects of RGPS on the levels of cytokines such as IL-1β, IL-6 and GM-CSF were measured using emzyme-linked immunospecific assay (ELISA). The mRNA expression levels of cytokines, enzymes (HDC2, COX-1, COX-2 and 5LO) and FcεRI αβγ subunits were measured using reverse transcription polymerase chain reaction (RT-PCR) method. The activation of FcεRI-mediated signaling was examined using Western blot analyses. Results: RGPS suppressed production of pro-inflammatory cytokines (IL-1β, IL-6, and GM-CSF) in stimulated RBL-2H3 cells significantly (p < 0.05). RGPS also suppressed mRNA expression of inflammatory enzymes (HDC2, COX-1, COX-2, 5LO). In addition, mRNA expression levels of FcεRIα, FcεRIβ and FcεRIγ were lowered by treatment with RGPS. Finally, RGPS prevented phosphrylation of Lyn, Syk, LAT, Gab2, PLCγ1/2, PI3K, Akt, cPLA2 and IκBα. Conclusion: RGPS effectively suppresses mast cell activations such as degranulation and inflammatory response via down-regulation of the FcεRI-mediated signaling pathways in IgE/Ag-stimulated mast cells.
참고문헌 (32)
- Stone KD., "IgE, mast cells, basophils, and eosinophils", J Allergy Clin Immunol, 125(2 Suppl 2), pp.S73~S80 (2010)
- Stassen M., "Murine bone marrow-derived mast cells as potent producers of IL-9 : costimulatory function of IL-10 and kit ligand in the presence of IL-1", J Immunol, 164(11), pp.5549~5555 (2000)
- Hu. ltner L., "In activated mast cells, IL-1 upregulates the production of several Th2-related cytokines including IL-9", J Immunol, 164(11), pp.5556~5563 (2000)
- Kandere-Grzybowska K., "IL-1 induces vesicular secretion of IL-6 without degranulation from human mast cells", J Immunol, 171(9), pp.4830~4836 (2003)
- Lee SA., "Molecular regulation of interleukin-13 and monocyte chemoattractant protein-1 expression in human mast cells by interleukin-1", Am J Respir Cell Mol Biol, 31(3), pp.283~291 (2004)
- Subramanian N., "Interleukin 1 releases histamine from human basophils and mast cells in vitro", J Immunol, 138(1), pp.271~275 (1987)
- Kishimoto T., "INTERLEUKIN-6 : from basic science to medicine-40 years in immunology", Annu Rev Immunol, 23, pp.1~21 (2005)
- Walker C., "Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia", Am J Respir Crit Care Med, 150(4), pp.1038~1048 (1994)
- Saha S., "Granulocyte-macrophage colony-stimulating factor expression in induced sputum and bronchial mucosa in asthma and COPD", Thorax, 64(8), pp.671~676 (2009)
- Lamas AM., "Glucocorticoids inhibit eosinophil responses to granulocytemacrophage colony-stimulating factor", J Immunol, 147(1), pp.254~259 (1991)
- Hirata., "Expression of histidine decarboxylase messenger RNA and histamine N-methyltransferase messenger RNA in nasal allergy", Clin Exp Allergy, 29(1), pp.76~83 (1999)
- Reddy ST., "Genetic evidence for distinct roles of COX-1 and COX-2 in the immediate and delayed phases of prostaglandin synthesis in mast cells", Biochem Biophys Res Commun, 265(1), pp.205~210 (1999)
- Tanioka T., "Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis", J Biol Chem, 275(42), pp.32775~2782 (2000)
- M. Nakashima K., "Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and-2", J Biol Chem, 278(39), pp.37937~7947 (2003)
- Lewis RA., "Leukotrienes and other products of the 5-lipoxygenase pathway. biochemistry and relation to pathobiology in human diseases", N Engl J Med, 323(10), pp.645~655 (1990)
- Kinet J-P., "THE HIGH-AFFINITY IgE RECEPTOR(Fc RI) : from physiology to pathology", Annu Rev Immunol, 17(1), pp.931~972 (1999)
- Gilfillan AM., "Integrated signalling pathways for mast-cell activation", Nat Rev Immunol, 6(3), pp.218~230 (2006)
- Rivera J., "Molecular regulation of mast cell activation", J Allergy Clin Immunol, 117(6), pp.1214~1225 (2006)
- Vig M., "Calcium signaling in immune cells", Nat Immunol, 10(1), pp.21~27 (2009)
- Alvarez-Errico D., "Adapters in the organization of mast cell signaling", Immunol Rev, 232(1), pp.195~217 (2009)
- Yunkyung Han, "2,5-Dihydroxyacetophenone Isolated from Rehmanniae Radix Preparata Inhibits Inflammatory Responses in Lipopolysaccharide-Stimulated RAW264.7 Macrophages", Journal of Medicinal Food, 15(6), pp.505~510 (2012), 한국식품영양과학회[DOI]
- Liu CL., "Bioassay-guided isolation of antiinflammatory components from the root of Rehmannia glutinosa and its underlying mechanism via inhibition of iNOS pathway", J Ethnopharmacol, 143(3), pp.867~875 (2012)
- Lau TW., "Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer", J Ethnopharmacol, 123(1), pp.155~162 (2009)
- Baek GH., "Rehmannia glutinosa suppresses inflammatory responses elicited by advanced glycation end products", Inflammation, 35(4), pp.1232~1241 (2012)
- Sung YY., "Topical application of Rehmannia glutinosa extract inhibits mite allergen-induced atopic dermatitis in NC", Nga mice, 2011, pp.134(1), 37~44[DOI]
- MacGlashan DW., "Endocytosis, recycling, and degradation of unoccupied FcRI in human basophils", J Leukoc Biol, 82(4), pp.1003~1010 (2007)
- 강경화, "Inhibitory Effect of Rehmannia Glutinosa Pharmacopuncture Solution on β-hexosaminidase Release and Cytokine Production via FcεRI signaling in RBL-2H3 Cells", Journal of Pharmacopuncture, 14(2), pp.15~24 (2011), 대한약침학회
- Wu LC., "Immunoglobulin E receptor signaling and asthma", J Biol Chem, 286(38), pp.32891~2897 (2011)
- Nishiyama C., "Molecular mechanism of allergy-related gene regulation and hematopoietic cell development by transcription factors", Biosci Biotechnol Biochem, 70(1), pp.1~9 (2006)
- Garman SC., "The crystal structure of the human high-affinity IgE receptor(Fc RI)", Annu Rev Immunol, 17(1), pp.973~976 (1999)
- Gilfillan AM., "The tyrosine kinase network regulating mast cell activation", Immunol Rev, 228(1), pp.149~169 (2009)
- Kalesnikoff J., "New developments in mast cell biology", Nat Immunol, 9(11), pp.1215~1223 (2008)