EXPERIMENTAL PHOTOAGING IN C3H HEN, C3H/HEJ, AND BALB/C MICE - COMPARISON OF CHANGES IN EXTRACELLULAR-MATRIX COMPONENTS AND MAST-CELL NUMBERS/

Chronic exposure of human or murine skin to ultraviolet B (UVB) radiat ion alters dermal extracellular matrix composition and increases the n umber of mast cells and inflammatory cells. Experiments were designed to test the possible role of UVB-induced tumor necrosis factor-alpha i n these photoaging changes based on reports that C3H/HeN, but not C3H/ HeJ or Balb/c mice, produce excess TNF-alpha in response to UVB exposu re. Pigmented C3H/HeN and C3H/HeJ strains were exposed to a total of 7 5 J/cm(2) of UVB radiation, and unpigmented Balb/c mice were exposed t o 19 J/cm(2) The UVB-induced increases in collagen, glycosaminoglycans , and neutrophil number were similar or the same in all three strains. The elastin increase was greater in C3H/HeJ than in C3H/HeN mice. The most striking difference between the strains was a 7.7-fold UVB-induc ed increase in mast cells in C3H/HeN mice compared to no increase in i rradiated C3H/HeJ mice and a 2.3-fold increase in Balb/c mice. These r esults suggest that excess TNF-alpha (or other mediator) produced in C 3H/HeN skin (but not C3H/HeJ skin) in response to UVB exposure is invo lved in the mast cell increase and partial inhibition of elastin incre ase, but that neither these mediators nor mast cell products are impor tant mediators for the chronic UVB-induced increases in neutrophils, g lycosaminoglycans, and collagen. When a possible source of the excess TNF-alpha was investigated, it was found that isolated epidermal cells from all three strains produced increases in TNF-alpha in response to UVB radiation. These results, as well as the previous results showing differences between these strains in UVB-induced effects on cutaneous immune function, are consistent with a model in which UVB-induced med iators from the epidermis stimulate another cell type to produce exces s TNF-alpha (and other mediators) in the C3H/HeN but not C3H/HeJ or Ba lb/c mice.