Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Effect of Gefitinib on Immune Response of Human Peripheral Blood Monocyte-Derived Dendritic Cells

인간 말초혈액 단핵구 유래 수지상세포의 면역반응에 미치는 Gefitinib의 영향

  • Cho, Jin-Hoon (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Kim, Mi-Hyun (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Lee, Kwang-Ha (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Kim, Ki-Uk (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Jeon, Doo-Soo (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Park, Hye-Kyung (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Kim, Yun-Seong (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Lee, Min-Ki (Department of Internal Medicine, Pusan National University School of Medicine) ;
  • Park, Soon-Kew (Department of Internal Medicine, Pusan National University School of Medicine)
  • 조진훈 (부산대학교 의학전문대학원 내과학교실) ;
  • 김미현 (부산대학교 의학전문대학원 내과학교실) ;
  • 이광하 (부산대학교 의학전문대학원 내과학교실) ;
  • 김기욱 (부산대학교 의학전문대학원 내과학교실) ;
  • 전두수 (부산대학교 의학전문대학원 내과학교실) ;
  • 박혜경 (부산대학교 의학전문대학원 내과학교실) ;
  • 김윤성 (부산대학교 의학전문대학원 내과학교실) ;
  • 이민기 (부산대학교 의학전문대학원 내과학교실) ;
  • 박순규 (부산대학교 의학전문대학원 내과학교실)
  • Received : 2010.10.28
  • Accepted : 2010.12.16
  • Published : 2010.12.30
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Abstract

Background: Synergistic antitumor effects of the combined chemoimmunotherapy based on dendritic cells have been reported recently. The aim of this study is to search new applicability of gefitinib into the combination treatment through the confirmation of gefitinib effects on the monocyte derived dendritic cells (moDCs); most potent antigen presenting cell (APC). Methods: Immature and mature monocyte-derived dendritic cell (im, mMoDC)s were generated from peripheral blood monocyte (PBMC) in Opti-MEM culture medium supplemented with IL-4, GM-CSF and cocktail, consisting of TNF-${\alpha}$ (10 ng/mL), IL-$1{\beta}$ (10 ng/mL), IL-6 (1,000 U/mL) and $PGE_2$ ($1{\mu}/mL$). Various concentrations of gefitinib also added on day 6 to see the influence on immature and mature MoDCs. Immunophenotyping of DCs under the gefitinib was performed by using monoclonal antibodies (CD14, CD80, CD83, CD86, HLA-ABC, HLA-DR). Supernatant IL-12 production and apoptosis of DCs was evaluated. And MLR assay with $[^3H]$-thymidine uptake assay was done. Results: Expression of CD83, MHC I were decreased in mMoDCs and MHC I was decreased in imMoDCs under gefitinib. IL-12 production from mMoDCs was decreased under $10{\mu}M$ of gefitinib sinificantly. Differences of T cell proliferation capacity were not observed in each concentration of geftinib. Conclusion: In spite of decreased expressions of some dendritic cell surface molecules and IL-12 production under $10{\mu}M$ of gefitinib, significant negative influences of gefitinib in antigen presenting capacity and T cell stimulation were not observed.

Keywords

References

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