過去實驗研究發現，在加入PMA誘導形成巨噬細胞的HEL細胞中，再加入前列腺環素致效劑(prostacyclin agonist)會使細胞進一步分化形成棘狀細胞(dendritic cell)，並且表現棘狀細胞的表面抗原。而在單純的HEL細胞中，加入前列腺環素致效劑則會使細胞生長族群在S期減少而在G0/G1期增加。對於前列腺環素致效劑在同一株細胞中，由於PMA是否參與，進而影響前列腺環素致效劑對細胞生理現象上的改變，其中所造成訊息傳遞的不同，便是本研究主要探討的部分。
　　我們發現MEK抑制劑U0126會抑制前列腺環素致效劑誘導前處理PMA的HEL細胞形成棘狀細胞，由於訊息傳遞途徑中，MEK下游為ERK (extracellular regulated kinase)，進一步我們便探討前列腺環素致效劑所誘導ERK1/2磷酸化，其訊息傳遞在有無PMA的情況下有何差異。
　　實驗結果得知，IP致效劑100nM BMY 45778所產生的訊息傳遞途徑在單純的HEL細胞中及PMA-pretreated HEL細胞中均有MEK-dependent
PKC-dependent、PKA-independent之現象。其中唯一的相異處則在PI3K相關的訊息傳遞途徑以及ERK1/2磷酸化維持時間的長短。在單純的HEL細胞中，IP致效劑100nM BMY 45778誘導ERK1/2磷酸化維持時間為30分鐘，且有PI3K-dependent現象產生，進而誘導PI3K下游的分子GSK3ß磷酸化，IP致效劑100nM BMY 45778誘導GSK3ß磷酸化的訊息傳遞為MEK-independent、PKA-dependent及PKC-dependent。而在PMA-pretreated HEL細胞中IP致效劑100nM BMY 45778誘導ERK1/2磷酸化維持時間為4小時以上，且為PI3K-independent，而其對於PI3K下游的分子GSK3ß磷酸化未有任何影響，顯示在PMA-pretreated HEL細胞中，IP接受體活化之訊息傳遞途徑中，確實未有PI3K的參與。

　Previously, studies using the 24 hours PMA-pretreated HEL cells (human erythroleukemia cell), prostacyclin induced the cells to develope the characteristic of dendritic cells (DC). Further characterization of these cells concluded that prostacyclin agonist BMY45778 induces DC differentiation from PMA-pretreated HEL cells, with phenotypic changes to CD83+ HLA-DR+. However, treatment of HEL cells with only prostacyclin agonist BMY45778 without PMA pretreatment results in an accumulation of HEL cells in the G0/G1 phase while decreases the number of cells in S phases. Since prostacyclin agonist BMY45778 induced different consequence in the presence or absence of PMA, we were interested to study the changes in the signaling events induced by prostacyclin before and after phorbol ester treatment of HEL cells.
　We found that MEK inhibitor U0126 prevented dendritic cell differentiation induced by prostacyclin after phorbol ester treatment of HEL cells. Since the downstream effector of MEK kinase is ERK1/2 (extracellular regulated kinase), we further studied the change of ERK1/2 phosphorylation induced by prostacyclin after phorbol ester treatment of HEL cells.
　Prostacyclin agonist BMY45778 induced ERK1/2 phosphorylation were PKC-dependent but PKA-independent in both untreated and PMA-pretreated HEL cells. The only difference between them was the duration of ERK1/2 phosphorylation and the involvement of PI3K pathway. In untreated HEL cells, BMY45778 induced PI3K-dependent ERK1/2 phosphorylation and the duration of ERK1/2 phosphorylation was thirty minutes. BMY45778 also induced the phosphorylation of GSK3β, the downstream effector of PI3K, which was MEK-independent, PKA-dependent and PKC-dependent. However on PMA-pretreated HEL cells, BMY45778 induced ERK1/2 phosphorylation was PI3K-independent and lasted for four hours, while the phosphorylation of GSK3β was not affected. Therefore, the signal pathway induced by BMY45778 in PMA-pretreated HEL cells is PI3K independent.

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