Increased Basal Transepidermal Water Loss Leads to Elevation of Some but Not All Stratum Corneum Serine Proteases

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.