Modulation of immune functions by TCDD and PCB in B cells = B 세포에서 TCDD와 PCB가 면역기능 조절에 미치는 영향에 관한 연구

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Halogenated aromatic hydrocarbons (HAHs) are ubiquitous contaminants in our environment and many of their toxic effects are elicited by binding to the aryl hydrocarbon receptor (AhR). However, several investigations have demonstrated that certain polychlorinated biphenyl (PCB) congeners or mixtures inhibit AhR-mediated responses induced by other toxic HAHs. The mechanism responsible for antagonism by certain PCBs of AhR-mediates biological activity is presently unknown. The present study evaluated the antagonist activity of several di-ortho-substituted PCB congeners [PCB47 (2,2’,4,4’), PCB52 (2,2’,5,5’), PCB128 (2,2’,3,3’,4,4’), PCB153 (2,2’,4,4’,5,5’)], when present in combination with AhR agonists [TCDD (2,3,7,8,-tetrachlorodibenzo-p-dioxin), PCB126 (3,3’,4,4’,5), PCB77 (3,3’,4,4’)], on CYP1A1 induction and inhibition of LPS-induced immunoglobulin production in the CH12.LX B cell line. In contrast to non-ortho-substituted PCB (PCB77), which showed additive effects on CYP1A1 induction in combination with TCDD, all of the di-ortho-substituted PCBs examined produced antagonism. Di-ortho-substituted PCB (PCB52) also partially antagonized TCDD- or PCB126-mediated inhibition of IgM secretion and immunoglobulin heavy chain mRNA expression in the LPS-activated B cells. In addition, PCB52 inhibited TCDD-induced nuclear translocation of AhR and subsequently DNA binding to a dioxin responsive element (DRE) in the B cell line. Collectively, these results suggest that the mechanism responsible for antagonism by di-ortho-substituted PCB congeners of AhR agonist-mediated CYP1A1 induction and inhibition of antibody responses in B cells occurs through interference with activation by agonist of the cytosolic AhR complex. TCDD produces a significant inhibition of IgM expression in B cells. However, the mechanism responsible for this inhibition is still unclear. The present study examined the effect of TCDD on AP-1 and $NF-\kappaB$, both of which play an important role in B...
Advisors
Yang, Kyu-Hwan양규환
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
2002
Identifier
174553/325007 / 000975164
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생물과학과, 2002.2, [ ix, 87 p. ]

Keywords

Immunomodulation; TCDD; PCB; 길항성; AhR; Antagonism; 다이옥신; 면역기능조절; 폴리염화페닐; 다이옥신 수용체

URI
http://hdl.handle.net/10203/27524
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=174553&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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