| Summary: | 博士 === 高雄醫學大學 === 醫學研究所 === 98 === Dendritic cells (DCs) are the major antigen-presenting cells involved in the induction of the primary immune response and play a critical role in immunity, but the mechanisms through which DCs are regulated remain incompletely defined. To this end, in may thesis work, the effects of endocrine-disrupting chemicals (EDCs) and cAMP activators on the function of human plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were evaluated. Environmental chemicals and pollutants, including EDCs are suggested to be important for the expression of allergic diseases. DCs, one of the front-line cell types in contact with environment, are potentially a critical cell target for modulation. We found that two common EDCs, nonylphenol (NP) and 4-octylphenol (4-OP) are able to induce, at the physiological doses, the expression of TNF-α in mDCs via enhancing MAPK signaling pathway and epigenetic pathways involving histone modifications, with subsequent influence on the T-cell cytokine responses. We have also studied the effect of a cAMP activator, prostaglandin (PG) I2 analogs, on the function of pDCs. We discovered that iloprost, a PGI2 analog, is capable of enhancing IL-10 and suppressing TLR-mediated TNF-α and IFN-α production of human pDCs via the IP receptor and, in part, the cAMP pathway. These studies suggest, therefore, that EDCs may induce inflammatory cytokine and suppress anti-inflammatory cytokine expression in mDCs, while, PGI2 analogs may have anti-inflammatory effect on pDCs. The two seemingly, independent pathways mediated by EDCs and cAMP-activating agents, respectively, in DCs may thus represent a novel regulatory mechanism by which DC’s innate function and subsequent adaptive immunity can be modulated, thereby influencing ultimately the expression of diseases.
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