點帶石斑魚 (Epinephelus coiodes) 是台灣重要的經濟養殖魚類之一，但緊迫 (stress) 的發生影響魚體對免疫反應的調控及在水產養殖的產量。本研究目的了解在緊迫下，透過分析皮質醇 (cortisol) 途徑活化對發炎反應前細胞激素腫瘤壞死因子α1 (tumor necrosis factor α1, osgTNFα1) 之調控。首先，發現在緊迫下皮質醇接受器 2 (glucocorticoid receptor 2, osgGR2) 及熱休克蛋白90AB (heat shock protein 90 AB, osgHSP90AB) 與 osgTNFα1 基因表現量呈現相反表現的趨勢。在石斑魚魚鰭細胞 (GF-1 cell line) 証實皮質醇結合或 NNV 感染造成皮質醇途徑的活化下，可使 osgGR2 具有 trans-activation 的能力；並在相同處理下證實 osgGR2 具有 trans-repression 的能力，並可抑制發炎前細胞激素 osgTNFα1 啟動子的表現；在相同處理下，藉由 N/C ratio 的分析，證實皮質醇及 NNV 感染皆可促使 osgGR2 進入細胞核量增加；以 FRET 證實 osgHSP90AB 參與調控 osgGR2 活性當中；利用基因刪除證實 osgGR2 具有區域專一性，且以轉錄活性位影響轉錄活性最大。總結，在緊迫下可活化點帶石斑魚皮質醇途徑，證實 osgGR2 可受到皮質醇活化且具轉錄活性，並參與調控發炎前細胞激素腫瘤壞死因子。

Orange-spotted grouper (Epinephelus coiodes) is one of the important aquaculture fish in Taiwan. However, stress will decrease the immunity of the grouper and the production. Our aim is to understand the characterization of glucocorticoid pathway involved in modulating inflammation cytokine under stress condition. First, we found that the opposite gene expression of glucocorticoid receptor 2 (osgGR2) / heat shock protein 90 AB (osgHSP90AB) and tumor necrosis factor α1 (osgTNFα1) under stress condition. Transcription activity analysis explained that osgGR2 has the trans-activation ability to promote GRE-target gene activation under cortisol treatment and be regulated by NNV. Furthermore, osgGR2 has trans-repression activity to inhibit osgTNFα1 promoter expression and entered the nucleus under stress by N/C ratio calculation. The trans-activation domain of osgGR2 has the ability to influence promoter activity using gene deletion. Using FRET experiment had explained how cortisol exerts their influences to regulate genes by binding to the grouper osgGR2 and dissociating with osgHSP90AB. These findings suggesting the biological effects of cortisol/osgGR2 pathway involve in inhibition of pro-inflammation cytokine osgTNFα1 promoter under stress condition in orange-spotted grouper.

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