UV light B-mediated inhibition of skin catalase activity promotes Gr-1+ CD11b+ myeloid cell expansion.
Skin cancer incidence and mortality are higher in men compared with women, but the causes of this sex discrepancy remain largely unknown. UV light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1(+)CD11b(+) myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis. Reduced activity of catalase, an antioxidant present in the skin, has been associated with skin carcinogenesis. We used the outbred, immune-competent Skh-1 hairless mouse model of UVB-induced inflammation and non-melanoma skin cancer to further define sex discrepancies in UVB-induced inflammation. Our results demonstrated that male skin had relatively lower baseline catalase activity, which was inhibited following acute UVB exposure in both sexes. Further analysis revealed that skin catalase activity inversely correlated with splenic Gr-1(+)CD11b(+) myeloid cell percentage. Acute UVB exposure induced Gr-1(+)CD11b(+) myeloid cell skin infiltration, which was inhibited to a greater extent in male mice by topical catalase treatment. In chronic UVB studies, we demonstrated that the percentage of splenic Gr-1(+)CD11b(+) myeloid cells was 55% higher in male tumor-bearing mice compared with their female counterparts. Together, our findings indicate that lower skin catalase activity in male mice may at least in part contribute to increased UVB-induced generation of Gr-1(+)CD11b(+) myeloid cells and subsequent skin carcinogenesis.
Department of Pathology, The Ohio State University, 302B Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
Nicholas J
NJ
Sullivan
Kathleen L
KL
Tober
Erin M
EM
Burns
Jonathan S
JS
Schick
Judith A
JA
Riggenbach
Thomas A
TA
Mace
Matthew A
MA
Bill
Gregory S
GS
Young
Tatiana M
TM
Oberyszyn
Gregory B
GB
Lesinski
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002374:Catalase / Q000528:radiation effects*; D049109:Cell Proliferation; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D022423:Myeloid Cells / Q000201:enzymology / Q000473:pathology* / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000473:pathology; D019707:Receptors, Chemokine / Q000378:metabolism; D012737:Sex Factors; D012867:Skin / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000473:pathology; D014466:Ultraviolet Rays
D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D002374:Catalase