Inhibitory effects of mizolastine on ultraviolet B-induced leukotriene B4 production and 5-lipoxygenase expression in normal human dermal fibroblasts in vitro.
Ultraviolet B (UVB) irradiation exerts hazardous effects such as acute photodamage, skin cancer and photoaging. In this study we evaluated the protective effects of a nonsedative histamine H1-receptor antagonist, mizolastine, on UVB-exposed skin dermal fibroblasts. Therefore, primary human skin fibroblasts were incubated with mizolastine or dexamethasone after 100 mJ/cm(2) UVB irradiation. Leukotriene B4 (LTB4) in fibroblast supernatants was detected with enzyme immunoassays, expression of 5-lipoxygenase (5-LOX) messenger RNA (mRNA) in skin fibroblasts was examined by reverse transcriptase-polymerase chain reaction and expression of 5-LOX protein was measured by immune blotting and immunofluorescent staining with rabbit anti-human 5-LOX antibody. It was found that 0.01 mM mizolastine inhibited UVB-induced LTB4 production from skin fibroblasts at 12, 24 and 36 h. Meanwhile, mizolastine down-regulated 5-LOX mRNA expression and inhibited 5-LOX translocation from nucleus to cytoplasm in fibroblasts. On the basis of these findings, we propose that mizolastine might play a protective role in the pathogenesis of UV radiation-induced acute photodamage of the skin.
Yan
Yan
Y
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Wang
Baoxi
B
Zuo
Ya-Gang
YG
Qu
Tao
T
D001562:Benzimidazoles / Q000494:pharmacology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis; D008084:Lipoxygenase / Q000235:genetics; D011837:Radiation-Protective Agents / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D001562:Benzimidazoles; D011837:Radiation-Protective Agents; D007975:Leukotriene B4; C076170:mizolastine; D008084:Lipoxygenase