RESUMEN
The predominant cyclooxygenase products of keratinocytes are prostaglandin (PG)E2 and PGF2 alpha with only trace amounts of PGI2 synthesis detected. When normal or immortal (NM1) keratinocytes were co-cultured with mitomycin C-treated 3T3 cells, increased synthesis of PGI2 was noted compared to mitomycin C-treated 3T3 cells alone. The PGI2 level in co-cultures was maximum within the first week and diminished rapidly thereafter. These results suggested keratinocytes enhance the production of PGI2 by 3T3 cells. Keratinocyte cultures incubated with Iloprost and Piriprost, stable PGI2 analogues, showed evidence of increased cornification as demonstrated by staining with rhodanile blue, decreased shedding of cells into the culture medium, and more cornified material adhering to the culture surface. The cultures appeared to be responsive between the first and second weeks after plating and the inhibition of shedding could not be reversed by changing to drug-free medium. Control and treated cultures showed identical electrophoretic protein patterns. Immunoblots showed involucrin unchanged in extracts of control and treated cultures while the 22 kd pancornulin was absent in treated cultures. The findings that keratinocytes enhance the production of PGI2 by 3T3 cells and that PGI2 analogues enhance cornification of confluent keratinocytes raise the possibility that eicosanoids may serve as autoregulatory signals together with other factors.
Asunto(s)
Células 3T3/metabolismo , Epoprostenol/biosíntesis , Queratinocitos/citología , 6-Cetoprostaglandina F1 alfa/metabolismo , Animales , Ácido Araquidónico/farmacología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Humanos , Iloprost/farmacología , Técnicas In Vitro , Ratones , Mitomicina/farmacología , Vitamina A/farmacologíaRESUMEN
1. A monoclonal antibody (HCE-2) to human epidermal and epithelial cornified envelopes identified a group of soluble basic protein precursors. 2. Using HCE-2, envelope-like staining was observed in the epidermis and stratified squamous epithelium of a number of mammalian species. 3. Basic polypeptides reactive to HCE-2 varied in size and number among the different animals. 4. In those species studied, HCE-2-reactive peptides were substrates for transglutaminase and protease treatment of cornified envelopes released HCE-2-reactive degradation products. 5. These results suggest a new family of proteins in mammalian epidermis that may function as cornified envelope precursors.