Regulation of epidermal cell interleukin-6 production by UV light and corticosteroids.
Epidermal cells (EC) are well known as a source of cytokines, including interleukin (IL)-6. In the present study, we investigated whether ultraviolet (UV) light and corticosteroids (CS) affect IL-6 production by normal (HNK) or malignant (KB) human keratinocytes. Supernatants derived from UVB (100 J/m2)- but not from UVA (100-1500 kJ/m2)-exposed EC (HNK and KB) contained significantly increased levels of IL-6 activity. This was also confirmed by Western blot analysis, resulting in specific bands at 23 kD and 27 kD. Northern blot analysis revealed an enhanced IL-6 mRNA expression after UVB exposure. Addition of hydrocortisone, prednisolone, or dexamethasone immediately after UVB irradiation significantly blocked UVB or IL-1-induced IL-6 mRNA expression and production by EC. The suppressive effect was observed at doses in the physiologic (10(-7)-10(-9) M) as well as pharmacologic (10(-5)-10(-7) M) range. In contrast, the nonactive steroid prednisone did not affect EC IL-6 mRNA expression. These findings indicate that increased IL-6 production by EC after UVB irradiation may mediate local and systemic inflammatory reactions following extensive sun exposure. Thus, the therapeutic effect of corticosteroids observed in various inflammatory diseases may be partly due to their downregulating capacity of IL-6 production.
Kirnbauer
R
R
Department of Dermatology II, University of Vienna, Austria.
Köck
A
A
Neuner
P
P
Förster
E
E
Krutmann
J
J
Urbanski
A
A
Schauer
E
E
Ansel
J C
JC
Schwarz
T
T
Luger
T A
TA
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007624:KB Cells / Q000528:radiation effects; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D000305:Adrenal Cortex Hormones; D015850:Interleukin-6; D003907:Dexamethasone