Expression of the tumor necrosis factor gene by dermal fibroblasts in response to ultraviolet irradiation or lipopolysaccharide.
To examine the effects of different wavelengths of ultraviolet (UV) radiation on tumor necrosis factor (TNF) production, we took advantage of mice carrying a chloramphenicol acetyl transferase (CAT) reporter transgene bearing the entire TNF promoter and 3'-untranslated region. Aside from constitutive expression in the thymus, CAT activity was detected only in locally UVB- or UVC-irradiated skin. After UVB irradiation, markedly greater amounts of CAT activity were traced to the dermis rather than the epidermis; by contrast, almost all CAT activity was localized to the epidermis after UVC irradiation. Fibroblasts have not been shown previously to express the TNF gene, i.e., the TNF gene is highly methylated and inaccessible to exogenous modulation in 3T3 fibroblasts. However, the present report reveals that cultured dermal fibroblasts are capable of producing both CAT and TNF in response to treatment in vitro with either UVB irradiation, UVC irradiation, or lipopolysaccharide. These findings indicate that dermal fibroblasts may serve not only as a target for but also as a source of TNF.
de Kossodo
S
S
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9050.
Cruz
P D
PD
Dougherty
I
I
Thompson
P
P
Silva-Valdez
M
M
Beutler
B
B
D000818:Animals; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004817:Epidermis / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects*; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase