SerpinB2 Deficiency Results in a Stratum Corneum Defect and Increased Sensitivity to Topically Applied Inflammatory Agents
| Autor: | Thiago Dominguez Crespo Hirata, Itaru Anraku, Thuy T. Le, Lee Major, Jonathan Ellis, Andreas Suhrbier, Wayne A. Schroder, Helder I. Nakaya |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Keratinocytes
0301 basic medicine Immunoblotting Pharmacology Protein degradation Dermatitis Contact Pathology and Forensic Medicine Cornified envelope Mice 03 medical and health sciences Plasminogen Activator Inhibitor 2 medicine Stratum corneum Animals Barrier function Skin Mice Knockout Transepidermal water loss integumentary system Chemistry Immunohistochemistry Urokinase-Type Plasminogen Activator 030104 developmental biology medicine.anatomical_structure Plasminogen activator inhibitor-2 Immunology Female Wound healing Keratinocyte |
| Zdroj: | The American Journal of Pathology. 186:1511-1523 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2016.02.017 |
| Popis: | SerpinB2 (plasminogen activator inhibitor type 2) is constitutively expressed at high levels by differentiating keratinocytes in mice and humans; however, the physiological function of keratinocyte SerpinB2 remains unclear. Herein, we show that SerpinB2 −/− mice are more susceptible to contact dermatitis after topical application of dinitrofluorobenzene, and show enhanced inflammatory lesions after topical applications of phorbol ester. Untreated SerpinB2 −/− mice showed no overt changes in epithelial structure, and we were unable to find evidence for a role for keratinocyte SerpinB2 in regulating immunity, apoptosis, IL-1β production, proteasomal activity, or wound healing. Instead, the phenotype was associated with impaired skin barrier function and a defective stratum corneum, with SerpinB2 −/− mice showing increased transepidermal water loss, increased overt loss of stratum corneum in inflammatory lesions, and impaired stratum corneum thickening after phorbol ester treatment. Immunoblotting suggested that SerpinB2 (cross-linked into the cornified envelope) is present in the stratum corneum and retains the ability to form covalent inhibitory complexes with urokinase. Data suggest that the function of keratinocyte SerpinB2 is protection of the stratum corneum from proteolysis via inhibition of urokinase, thereby maintaining the integrity and barrier function of the stratum corneum, particularly during times of skin inflammation. Implications for studies involving genetically modified mice treated with topical agents and human dermatological conditions, such as contact dermatitis, are discussed. |
| Databáze: | OpenAIRE |
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