siRNA-mediated knock-down of COX-2 in melanocytes suppresses melanogenesis
siRNA-mediated knock-down of COX-2 in melanocytes suppresses melanogenesis
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DOI：
10.1111/j.1600-0625.2012.01483.x
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发表时间：
2012-06-01
影响因子：
3.6
通讯作者：
Oh, Sang H.
中科院分区：
文献类型：
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作者：
Kim, Ji Y.;Shin, Jae Y.;Oh, Sang H.
环氧合酶-2（考克斯-2）是响应于多种促有丝分裂和炎症刺激（包括UV光）而诱导的酶。UV诱导的考克斯-2表达诱导角质形成细胞产生前列腺素E2（PGE 2），其介导炎症和细胞增殖。直到最近，关于皮肤中的考克斯-2和PGE 2的研究一直集中在角质形成细胞和皮肤癌以及角质形成细胞产生的PG对黑素细胞的影响上。然而，考克斯-2本身或考克斯-2抑制剂对黑素生成的作用还不清楚。因此，为了确定考克斯-2在黑素生成中的作用，我们研究了通过用考克斯-2短干扰RNA（siRNA）沉默考克斯-2表达来敲低黑素细胞中的考克斯-2对黑素生成和黑素生成分子表达的影响。考克斯-2基因敲低可降低黑素细胞酪氨酸酶、TRP-1、TRP-2、gp 100和MITF的表达，同时也降低酪氨酸酶活性。此外，考克斯-2 siRNA转染的黑素细胞显示出显著减少α-黑素细胞刺激激素（α-MSH）诱导的黑素产生。此外，在乱序siRNA转染和考克斯-2 siRNA转染的黑素细胞中，α-MSH诱导的考克斯-2表达均大于α-MSH未处理的细胞。我们的研究结果表明，考克斯-2可能是一个候选目标的发展，抗黑素剂和α-MSH诱导的色素沉着可能与考克斯-2的表达密切相关。因此，考克斯-2抑制剂可能在用于色素沉着过度疾病如黄褐斑、炎症后色素沉着过度和日光性雀斑的美白化妆品中特别有用。
Cyclooxygenase-2 (COX-2) is an enzyme induced in response to multiple mitogenic and inflammatory stimuli, including UV light. UV-induced COX-2 expression induces production of prostaglandin E2 (PGE2) in keratinocytes, which mediates inflammation and cell proliferation. Until recently, studies regarding COX-2 and PGE2 in the skin have focused on keratinocytes and skin cancer and the effect of PGs produced by keratinocytes on melanocytes. However, the effects of COX-2 itself or COX-2 inhibitors on melanogenesis are not well known. Therefore, to establish the role of COX-2 in melanogenesis, we investigated the effects of knock-down of COX-2 in melanocytes on melanin production and the expression of melanogenic molecules through silencing of COX-2 expression with COX-2 short interfering RNA (siRNA). COX-2 knock-down in melanocytes decreased the expressions of tyrosinase, TRP-1, TRP-2, gp100 and MITF and also reduced tyrosinase enzyme activity. Furthermore, COX-2 siRNA-transfected melanocytes showed markedly reduced alpha-melanocyte stimulating hormone (a-MSH)-induced melanin production. In addition, a-MSH-induced COX-2 expression in both scrambled siRNA-transfected and COX-2 siRNA-transfected melanocytes was greater than a-MSH-untreated cells. Our results suggest that COX-2 might be a candidate target for the development of anti-melanogenic agents and a-MSH-induced pigmentation could be closely associated with COX-2 expression. COX-2 inhibitors might therefore be of particular use in whitening cosmetics for hyperpigmentation disorders such as melasma, postinflammatory hyperpigmentation and solar lentigo.