Augmentation of lipogenesis by 15-deoxy-Δ12,14-prostaglandin J2 in hamster sebaceous glands:: Identification of cytochrome P-450-mediated 15-deoxy-Δ12,14-prostaglandin J2 production
Augmentation of lipogenesis by 15-deoxy-Δ12,14-prostaglandin J2 in hamster sebaceous glands:: Identification of cytochrome P-450-mediated 15-deoxy-Δ12,14-prostaglandin J2 production
复制标题
DOI：
10.1111/j.0022-202x.2005.23866.x
复制
发表时间：
2005-11-01
影响因子：
6.5
通讯作者：
Ito, A
中科院分区：
文献类型：
--
作者：
Iwata, C;Akimoto, N;Ito, A
前列腺素（PGs）在生理和病理条件下对皮肤细胞功能的调节起重要作用。在这项研究中，我们研究了前列腺素在体内和体外使用非甾体抗炎药的皮脂腺细胞脂肪生成的参与。耳廓皮脂腺细胞自发分化，积累胞内三酰甘油（TG），在此过程中15-deoxy-Delta（12，14）-PGJ（2）（15 d-PGJ（2））与PGF（2 α）和PGE（2）的相对水平增加。发现15 d-PGJ（2）增加脂滴的形成，这是由于二酰基甘油酰基转移酶（DGAT）增加TG合成。此外，在体内和体外，皮脂腺细胞组成型产生环氧合酶2（考克斯-2），但不产生考克斯-1。当用考克斯抑制剂如吲哚美辛、双氯芬酸或NS-398处理皮脂腺细胞时，PGF（2 α）和PGE（2）的产生减少。然而，15 d-PGJ 2的产生在这些经类固醇处理的皮脂腺细胞中增加。此外，吲哚美辛，双氯芬酸，NS-398增加TG的合成沿着DGAT活性的增加。同样，局部给药吲哚美辛仓鼠耳廓引起皮脂腺的发展，增加体内皮脂沉积。此外，吲哚美辛和NS-398增强的15 d-PGJ 2的产生和TG合成被非选择性细胞色素P-450（CYP 1A 1）抑制剂SKF-525 A抑制。过氧化物酶体增殖激活受体γ（PPAR γ）的配体激活剂，曲格列酮诱导的TG合成，然而，即使在SKF-525 A的存在下也没有改变。这些结果表明，15 d-PGJ 2是一个重要的刺激皮脂细胞脂肪生成通过增加DGAT介导的合成TG。除了PG合成的考克斯-2依赖性途径外，我们的研究结果还表明，通过抑制考克斯-2，可诱导皮脂腺细胞特异性途径产生15 d-PGJ（2）。
Prostaglandins (PGs) play important roles in the regulation of cutaneous cell functions under physiological and pathological conditions. In this study, we examined the involvement of PGs in sebocyte lipogenesis using nonsteroidal anti-inflammatory drugs in vivo and in vitro. Hamster auricle sebocytes spontaneously differentiated to accumulate intracellular triacylglycerol (TG), under which the relative levels of 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) to PGF(2 alpha) and PGE(2) increased. 15d-PGJ(2) was found to augment the formation of lipid droplets, which was because of an increase of TG synthesis by diacylglycerol acyltransferase (DGAT). Furthermore, sebocytes constitutively produced cyclooxygenase 2 (COX-2), but not COX-1, in vivo and in vitro. When sebocytes were treated with COX inhibitors such as indomethacin, diclofenac, or NS-398, the production of PGF(2 alpha) and PGE(2) decreased. The production of 15d-PGJ2, however, was increased in these inhibitor-treated sebocytes. In addition, indomethacin, diclofenac, and NS-398 augmented the synthesis of TG along with the increase in DGAT activity. Similarly, topical administration of indomethacin to hamster auricles caused the development of sebaceous glands with the augmentation of sebum deposition in vivo. Furthermore, indomethacin and NS-398-augmented 15d-PGJ2 production and TG synthesis were suppressed by a non-selective cytochrome P-450 (CYP) inhibitor, SKF-525A. A ligand activator of peroxisome proliferation activating receptor gamma (PPAR gamma), troglitazone-induced synthesis of TG, however, was not altered even in the presence of SKF-525A. These results suggest that 15d-PGJ2 is a crucial stimulator of sebocyte lipogenesis by augmenting DGAT-mediated synthesis of TG. In addition to the COX-2-dependent pathway of PG synthesis, our findings suggest a sebocyte-specific pathway of 15d-PGJ(2) production by CYP, the activity of which may be evoked by inhibiting COX-2.