본문 바로가기
KERD
논문KCI 등재

A549 기도 상피세포에서 GRβ의 과발현이 스테로이드에 의한 전체 유전자 변화에 미치는 영향

Effects of GRβ Overexpression on Steroid-induced Changes of the Whole Genes in the A549 Airway Epithelial Cells

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류임상병리학

초록

Background: Glucocorticoid receptor β (GRβ) may not bind to ligands and is thought to affect gene transcription only by acting as a dominant negative inhibitor of Glucocorticoid receptor α (GRα). However, there have been few reports about the functional roles of GRβ in the steroid-induces changes of gene expression. Objective: To investigate the functional role of GRβ overexpression in the steroid- induced changes of gene expression. Method: The changes in gene expressions such as steroid- induced synthesis of genes, TNF-α-induced synthesis of inflammatory genes and steroid induced suppression of activated genes by TNF-α treatment were compared with and without pCMV GRβ expression. Result: The number of genes increased by dexamethasonetreatment only in the GRβ transfected group were 54. Increased expressions of genes by dexamethasone treatment were not affected by GRβ overexpression. The number of genes increased by TNF-α treatment only in the GRβ-transfected group were 69. Expressions of genes increased by TNF-α treatment in both the control and the GRβ-transfected group were decreased by further dexamethasone treatment in a similar manner. Conclusion: The results of this study suggest that GRβ may not be a dominant negative inhibitor in the steroid- induced changes of genes and that it may have some functional roles in the regulation of gene expressions. (Korean J Asthma Allergy Clin Immunol 2008;28: 220-225)

Abstract

Background: Glucocorticoid receptor β (GRβ) may not bind to ligands and is thought to affect gene transcription only by acting as a dominant negative inhibitor of Glucocorticoid receptor α (GRα). However, there have been few reports about the functional roles of GRβ in the steroid-induces changes of gene expression. Objective: To investigate the functional role of GRβ overexpression in the steroid- induced changes of gene expression. Method: The changes in gene expressions such as steroid- induced synthesis of genes, TNF-α-induced synthesis of inflammatory genes and steroid induced suppression of activated genes by TNF-α treatment were compared with and without pCMV GRβ expression. Result: The number of genes increased by dexamethasonetreatment only in the GRβ transfected group were 54. Increased expressions of genes by dexamethasone treatment were not affected by GRβ overexpression. The number of genes increased by TNF-α treatment only in the GRβ-transfected group were 69. Expressions of genes increased by TNF-α treatment in both the control and the GRβ-transfected group were decreased by further dexamethasone treatment in a similar manner. Conclusion: The results of this study suggest that GRβ may not be a dominant negative inhibitor in the steroid- induced changes of genes and that it may have some functional roles in the regulation of gene expressions. (Korean J Asthma Allergy Clin Immunol 2008;28: 220-225)

참고문헌 (15)

  1. Muller M, "The glucocorticoid receptor. Biochim Biophys Acta", 1088, pp.171~182 (1991)
  2. Duma D, "Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification", J Steroid Biochem Mol Biol, 102, pp.11~21 (2006)
  3. Barnes PJ, "Molecular mechanisms of corticosteroids in allergic disease", Allergy, 56, pp.928~936 (2001)
  4. Gagliardo R, "Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma", Am J Respir Crit Care Med, 162, pp.7~13 (2000)
  5. Torrego A, "Glucocorticoid receptor isoforms alpha and beta in in vitro cytokine-induced glucocorticoid insensitivity", Am J Respir Crit Care Med, 170, pp.420~425 (2004)
  6. Gentleman RC, "Bioconductor: open software development for computational biology and bioinformatics", Genome Biol, 5, pp.R80~ (2004)
  7. Bolstad BM, "A comparison of normalization methods for high density oligonucleotide array data based on variance and bias", Bioinformatics, 22, pp.185~193 (2003)
  8. Irizarry RA, "Exploration, normalization, and summaries of high density oligonucleotide array probe level data", Biostatistics, 4, pp.249~264 (2003)
  9. Eisen MB, "Cluster analysis and display of genome-wide expression patterns", Proc Natl Acad Sci USA, 95, pp.14863~14868 (1998)
  10. Seo JH, "Effect of GRβ over-expression on steroid-induced suppression of IL-8 synthesis and secretion", Korean J of Asthma Allergy and Clin Immunol, 25, pp.123~129 (2005)
  11. Jee YK, "Effect of GRβ expression on Steroid-induced transcriptional activity in airway epithelial cells", Korean J of Asthma Allergy and Clin Immunol, 23, pp.810~817 (2003)
  12. Lewis-Tuffin LJ, "Human glucocorticoid receptor beta binds RU-486 and is transcriptionally active", Mol Cell Biol, 27, pp.2266~2282 (2007)
  13. Gagliardo R, "Is there a role for glucocorticoid receptor beta in asthma?", Respir Res, 2, pp.1~4 (2001)
  14. Strickland I, "High constitutive glucocorticoid receptor beta in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids", J Exp Med, 193, pp.585~593 (2001)
  15. Kelly A, "The glucocorticoid receptor beta isoform can mediate transcriptional repression by recruiting histone deacetylases", J Allergy Clin Immunol, 121, pp.203~208 (2008)

관련 논문AI추천

A549 기도상피세포에서 IL-8 전사와 분비에 미치는 Dexamethasone Troglitazone의 병합투여효과김남희, 김도형, 김윤섭, 박재석, 서지현, 이호연, 지영구, 한성환대한천식알레르기학회 · 천식 및 알레르기2008 · 제28권 제4호기도상피세포에서 GR 발현이 스테로이드에 의한 전사변화에 미치는 영향김윤섭, 박재석, 이계영, 지영구대한천식알레르기학회 · 천식 및 알레르기2003 · 제23권 제4호GRβ과발현이 스테로이드에 의한 IL-8 합성 및 분비에 미치는 영향곽상준, 김윤섭, 박재석, 서지희, 이계영, 이순일, 지영구대한천식알레르기학회 · 천식 및 알레르기2005 · 제25권 제2호상기도감염 후 악화된 기관지천식 환자의 말초혈액단핵구에서 glucocorticoid receptor beta의 발현유빈, 고수진, 김윤이, 문근애, 문희범, 서욱장, 이재천, 이창근, 이태훈, 조유숙대한천식알레르기학회 · 천식 및 알레르기2003 · 제23권 제3호스테로이드 의존성 천식 환자에서 스테로이드와 2-아드레날린 수용체 mRNA의 발현양상김상훈, 김세훈, 김우경, 김유영, 김윤근, 민경업, 반준우, 오선영, 장윤석, 조상헌대한천식알레르기학회 · 천식 및 알레르기2003 · 제23권 제2호Respiratory Syncytial Virus에 감염된 인간 기도 상피세포에서 RANTES 생산에 미치는 코르티코스테로이드의 영향이윤, 윤종서, 이은정, 이준성, 전혜진, 한지환대한 소아알레르기 호흡기학회 · Allergy Asthma & Respiratory Disease2005 · 제15권 제3호

이 간행물의 다른 논문 (11건)