A549 기도상피세포에서 IL-8 전사와 분비에 미치는 Dexamethasone Troglitazone의 병합투여효과
Effects of Co-treatment with Dexamethasone and Troglitazone on Transcription and Secretion of IL-8 in the A549 Airway Epithelial Cells
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Glucocorticoid is a widely used anti-inflammatory agent in a variety of diseases. Recently, peroxisome proliferator activated receptor γ (PPARγ) ligand has been shown to exert a potential anti-inflammatory activity, mainly through their ability to down- regulate pro-inflammatory gene expressions. Objective This study was designed to evaluate the effects of co-treatment with dexamethasone and troglitazone (a ligand of PPARγ) on IL-8 transcription and secretion. Method: Steroid and troglitazone-induced transactivation was measured by using pGRE luciferase reporter gene in the A549 cell line. Steroid-induced transrepression was measured by using stable A549 IgG-NFκB luciferase cell line, which contained the minimal IL-8 promoter region. Result: Co-treatment with dexamethasone and troglitazone showed no additional increase of transactivation activity compared to dexamethasone single treatment. Suppressions of the transcriptional activity in the IL-8 promotor and IL-8 secretion showed no difference in the co-treatment with dexamethasone and troglitazone compared to those in dexamethasone single treatment. Conclusion: Our results suggest that co-treatment with PPARγ ligand and steroid may not have an additive anti- inflammatory activity at least in the airway epithelial cell. (Korean J Asthma Allergy Clin Immunol 2008;28:292- 297)
Abstract
Background: Glucocorticoid is a widely used anti-inflammatory agent in a variety of diseases. Recently, peroxisome proliferator activated receptor γ (PPARγ) ligand has been shown to exert a potential anti-inflammatory activity, mainly through their ability to down- regulate pro-inflammatory gene expressions. Objective This study was designed to evaluate the effects of co-treatment with dexamethasone and troglitazone (a ligand of PPARγ) on IL-8 transcription and secretion. Method: Steroid and troglitazone-induced transactivation was measured by using pGRE luciferase reporter gene in the A549 cell line. Steroid-induced transrepression was measured by using stable A549 IgG-NFκB luciferase cell line, which contained the minimal IL-8 promoter region. Result: Co-treatment with dexamethasone and troglitazone showed no additional increase of transactivation activity compared to dexamethasone single treatment. Suppressions of the transcriptional activity in the IL-8 promotor and IL-8 secretion showed no difference in the co-treatment with dexamethasone and troglitazone compared to those in dexamethasone single treatment. Conclusion: Our results suggest that co-treatment with PPARγ ligand and steroid may not have an additive anti- inflammatory activity at least in the airway epithelial cell. (Korean J Asthma Allergy Clin Immunol 2008;28:292- 297)
참고문헌 (18)
- Muller M, "The glucocorticoid receptor", Biochem Biophys Acta, 1088, pp.171~182 (1991)
- Barnes PJ, "Molecular mechanisms of corticosteroids in allergic diseases", Allergy, 56, pp.928~936 (2001)
- Evans RM, "The steroid and thyroid hormone receptor superfamily", Science, 240, pp.889~895 (1988)
- Braissant O, "Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPARα,-β and -γ in the adult rat", Endocrinology, 137, pp.354~366 (1996)
- Escher P, "Peroxisome proliferator-activated receptor: insight into multiple cellular functions", Mutat Res, 448, pp.121~138 (2000)
- Spiegelman BM, "Adipogenesis and obesity: rounding out the big picture", Cell, 87, pp.377~389 (1996)
- Pawliczak R, "Wu T. 85-kDa cytosolic phospholipase A2 mediates peroxisome proliferator-activated receptor-γ activation in human lung epithelial cells", J Biol Chem, 277, pp.33153~33163 (2002)
- Wang ACC, "Peroxisome proliferator-activated receptor-γ regulates airway epithelial cell activation", Am J Respir Cell Mol Biol, 24, pp.688~694 (2001)
- Jiang C, "PPARγ agonists inhibit production of monocyte inflammatory cytokines", Nature, 391, pp.82~86 (1998)
- Kliewer SA, "Differential expression and activation of a family of murine peroxisome proliferator-activated receptors", Proc Natl Acad Sci USA, 91, pp.7355~7359 (1994)
- Kota BP, "An overview on biological mechanisms of PPARs", Pharmacol Res, 51, pp.85~94 (2005)
- Bailey ST, "‘PPAR'ting ways with inflammation", Nature Immunology, 6, pp.966~967 (2005)
- Casale TB, "Immunomodulators for allergic respiratory disorders", J Allergy Clin Immunol, 121, pp.288~296 (2008)
- Harada A, "Essential involvement of interleukin-8 (IL-8) in acute inflammation", J Leukoc Biol, 56, pp.559~564 (1994)
- Fujimura M, "Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin 8", Eur Respir J, 11, pp.306~311 (1988)
- Kurashima K, "Increase of chemokine levels in sputum precedes exacerbation of acute asthma attacks", J Leukoc Biol, 59, pp.313~316 (1996)
- Nonaka M, "GM-CSF, IL-8, IL-1R, TNF-αR and HLA-DR in nasal epithelial cells in allergic rhinitis", Am J Repir Crit Care Med, 153, pp.1675~1681 (1996)
- Marini M, "Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony- stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma", J Allergy Clin Immunol, 89, pp.1001~1009 (1992)