Voegeli R, Rawlings A V, Doppler S, Schreier T
DSM Nutritional Products Ltd, Branch Pentapharm, Engelgasse 109, 4002 Basel, Switzerland.
Int J Cosmet Sci. 2008 Dec;30(6):435-42. doi: 10.1111/j.1468-2494.2008.00472.x.
There are indications of elevation of some inflammatory serine proteases in barrier damaged skin (e.g. plasmin and urokinase). Moreover, many other serine protease activities are present such as desquamatory enzymes as well as a newly detected tryptase-like serine protease. However, the activities of these proteases have never been correlated with stratum corneum (SC) barrier function. The activity of extractable key serine proteases (SC trypsin-like kallikreins, SC chymotrypsin-like kallikreins, SC tryptase-like serine protease, urokinase and plasmin) was measured from the outermost layers of SC obtained from facial tape strippings in clinically normal subjects. The protein content of the tape strippings was quantified by absorption measurements with the novel infrared densitometer SquameScan 850A and the protease activities by the use of fluorogenic peptide substrates. SC barrier function, SC hydration and skin surface pH were measured using AquaFlux, NOVA dermal phase meter and Skin-pH-Meter, respectively. As expected, SC hydration was reduced with increased transepidermal water loss (TEWL) values indicative of barrier impairment. Surprisingly, SC chymotrypsin-like activity showed no correlation with hydration or TEWL, whereas all other enzymes positively correlated with impaired barrier function and some were statistically significant: SC trypsin-like kallikreins (R(2 )=0.66, P < 0.01), SC tryptase-like enzyme (R(2 )=0.95, P < 0.001), plasmin (R(2 )=0.86, P < 0.001) and urokinase (R(2 )=0.50, P < 0.05). All enzymes except urokinase also negatively correlated with SC hydration. Elevated levels of SC serine proteases have been associated with some dermatological disorders, such as atopic dermatitis, psoriasis and rosacea but these results indicate that these enzymes are also elevated with milder forms of barrier disruption, which is not clinically evident as irritated skin. As these proteases are elevated in the SC, they will also be elevated in the epidermis where they can be involved in neurogenic inflammation and epidermal barrier impairment via activation of the protease-activated receptors. These results highlight the need for using serine protease inhibitors especially for urokinase and plasmin, SC tryptase-like serine protease and possibly SC trypsin-like kallikreins even in milder forms of barrier damage.
有迹象表明，在屏障受损的皮肤中某些炎性丝氨酸蛋白酶会升高（例如纤溶酶和尿激酶）。此外，还存在许多其他丝氨酸蛋白酶活性，如脱屑酶以及一种新检测到的类胰蛋白酶丝氨酸蛋白酶。然而，这些蛋白酶的活性从未与角质层（SC）屏障功能相关联。从临床正常受试者面部胶带剥离获得的SC最外层中测量了可提取的关键丝氨酸蛋白酶（SC类胰蛋白酶激肽释放酶、SC类糜蛋白酶激肽释放酶、SC类胰蛋白酶丝氨酸蛋白酶、尿激酶和纤溶酶）的活性。通过使用新型红外密度计SquameScan 850A进行吸收测量来定量胶带剥离物的蛋白质含量，并通过使用荧光肽底物来测定蛋白酶活性。分别使用AquaFlux、NOVA皮肤相位仪和皮肤pH计测量SC屏障功能、SC水合作用和皮肤表面pH值。正如预期的那样，随着经表皮水分流失（TEWL）值增加表明屏障受损，SC水合作用降低。令人惊讶的是，SC类糜蛋白酶样活性与水合作用或TEWL无相关性，而所有其他酶与受损的屏障功能呈正相关，其中一些具有统计学意义：SC类胰蛋白酶激肽释放酶（R(2 ) = 0.66，P < 0.01）、SC类胰蛋白酶样酶（R(2 ) = 0.95，P < 0.001）、纤溶酶（R(2 ) = 0.86，P < 0.001）和尿激酶（R(2 ) = 0.50，P < 0.05）。除尿激酶外的所有酶也与SC水合作用呈负相关。SC丝氨酸蛋白酶水平升高与一些皮肤病有关，如特应性皮炎、银屑病和酒渣鼻，但这些结果表明，在屏障破坏较轻的情况下这些酶也会升高，而这种情况在临床上并不表现为皮肤刺激。由于这些蛋白酶在SC中升高，它们在表皮中也会升高，在表皮中它们可通过激活蛋白酶激活受体参与神经源性炎症和表皮屏障损伤。这些结果强调了使用丝氨酸蛋白酶抑制剂的必要性，特别是对于尿激酶和纤溶酶、SC类胰蛋白酶丝氨酸蛋白酶以及可能的SC类胰蛋白酶激肽释放酶，即使在屏障损伤较轻的情况下也是如此。
