Anti-inflammatory effects of tacalcitol (1,24(R)(OH)2D3, TV-02) in the skin of TPA-treated hairless mice.
Tacalcitol (1,24(R)(OH)2D3, TV-02) inhibited the TPA-induced inflammatory cell infiltration (largely neutrophils) histopathologically and myeloperoxidase (MPO) activity dose-dependently. Tacalcitol inhibited the mRNA expression and protein production of TPA-induced macrophage inflammatory protein-2 (MIP-2) and KC, the functional analogue of human interleukin (IL)-8, in the skin. Immunohistochemical staining of the TPA-applied skin revealed that mast cells expressed MIP-2, whereas KC was observed in keratinocytes, fibroblasts and outer root sheath of hair follicles. Furthermore, tacalcitol inhibited TPA-induced mast cell degranulation 24 hr after application without influence on the total number of mast cells. In this study, tacalcitol was found to have an inhibitory effect on cutaneous inflammation such as inhibition of neutrophil infiltration, MIP-2 and KC production, and mast cell degranulation in TPA-treated hairless mice. These results suggest that tacalcitol modulates cutaneous inflammation as well as keratinocyte proliferation and differentiation, and the inhibitory effect of tacalcitol on cutaneous inflammation may contribute to clinical the effectiveness in the treatment of psoriasis.
Sato
Hiroaki
H
Pharmacological Research Department, Pharmaceuticals Development Research Laboratories, Teijin Institute for Bio-Medical Research, Hino, Tokyo, Japan.
Nakayama
Yasunori
Y
Yamashita
Chizuru
C
Uno
Hiroshi
H
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001483:Base Sequence; D003872:Dermatitis / Q000188:drug therapy* / Q000473:pathology; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D018836:Inflammation Mediators / Q000032:analysis*; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008812:Mice, Hairless; D008969:Molecular Sequence Data; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate
D000893:Anti-Inflammatory Agents; D004100:Dihydroxycholecalciferols; D018836:Inflammation Mediators; C023850:1 alpha,24-dihydroxyvitamin D3; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate