Keratinocytes stimulate prostaglandin I2 synthesis by 3T3 cells and exhibit enhanced cornification when exposed to prostaglandin I2 analogues.
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.
Harvard Medical School, Department of Dermatology, Massachusetts General Hospital, Boston 02114.
H P
HP
Baden
M L
ML
Goldaber
J C
JC
Kvedar
D016475:3T3 Cells / Q000378:metabolism*; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology
D014801:Vitamin A; D016718:Arachidonic Acid; D016685:Mitomycin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D016285:Iloprost