Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin.
BACKGROUND
The biologically active vitamin D analog calcipotriol is effective and safe in the topical treatment of psoriasis, but its exact mechanism of action is unknown.


OBJECTIVE
We investigated expression of 1,25-dihydroxyvitamin D3 receptors, markers for inflammation (CD1a, CD4, CD8, CD11b, CD15; NAP-1/interleukin-8; 55 kd tumor necrosis factor-receptor; intercellular adhesion molecule-1; HLA-DR), proliferation (proliferating cell nuclear antigen, Ki-67), and differentiation (transglutaminase K; involucrin; cytokeratin 16) in psoriatic skin during topical calcipotriol treatment.


METHODS
For immunohistochemical staining we used the labeled avidin-biotin technique on cryostat-cut sections.


RESULTS
We found a significant increase of 1,25-dihydroxyvitamin D3 receptor expression in epidermal basal keratinocytes of lesional psoriatic skin during calcipotriol treatment. In all patients analyzed, effects on proliferation and differentiation of epidermal keratinocytes were stronger than effects on dermal inflammation. Effects on inflammation were more pronounced in the epidermal than in the dermal compartment.


CONCLUSIONS
Our findings indicate that analogs of 1,25-dihydroxyvitamin D3 upregulate their corresponding receptor in human keratinocytes in vivo. This mechanism may be important in the therapeutic efficacy of vitamin D analogs in psoriasis. The differential therapeutic effects in the epidermal and dermal skin compartments may be due to a reduced bioavailability of calcipotriol in the dermal compartment.
Reichrath
J
J
Department of Dermatology, University of the Saarland, Germany.
Müller
S M
SM
Kerber
A
A
Baum
H P
HP
Bahmer
F A
FA
D000279:Administration, Cutaneous; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D001682:Biological Availability; D018845:CD11 Antigens / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D007633:Keratins / Q000032:analysis; D016256:Lewis X Antigen / Q000032:analysis; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000648:ultrastructure; D018123:Receptors, Interleukin / Q000032:analysis; D023062:Receptors, Interleukin-8A; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D011503:Transglutaminases / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015854:Up-Regulation
D015703:Antigens, CD; D018949:Antigens, CD1; D018845:CD11 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D003879:Dermatologic Agents; D006684:HLA-DR Antigens; D016209:Interleukin-8; D016256:Lewis X Antigen; D018809:Proliferating Cell Nuclear Antigen; D011498:Protein Precursors; D018167:Receptors, Calcitriol; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C055085:calcipotriene; C032253:involucrin; D007633:Keratins; D011503:Transglutaminases; D002117:Calcitriol