Expression of integrin subunits and CD44 isoforms in psoriatic skin and effects of topical calcitriol application.
Increasing evidence suggests involvement of integrins and CD44 isoforms in the pathogenesis of psoriasis, contributing to uncontrolled keratinocyte proliferation, neovascularization, and invasion of inflammatory cells. We have analyzed immunohistochemically in situ expression of integrins (CD29, CDw49b, CDw49c, CDw49e, CDw49f) and CD44 isoforms (CD44 standard, CD44 var/v6, CD44 v10) on frozen sections of normal and psoriatic skin (nonlesional skin, lesional skin before and along with topical calcitriol treatment). We did not observe visual changes of immunoreactivity in normal as compared to nonlesional psoriatic skin, while the staining pattern of CDw49c, CDw49f, and CD29 was severely altered in untreated lesional psoriatic skin. Most markedly, CDw49c, CDw49f, and CD29 were focally upregulated in suprapapillar epidermal compartments of lesional psoriatic skin, a staining pattern that is in accordance with the phenomenon that was described by Pinkus as "squirting papilla". Additionally, an increased proportion of inflammatory and endothelial cells revealed immunoreactivity for CD44(std.) in untreated lesional psoriatic as compared to nonlesional psoriatic or normal skin. After 8 weeks of topical calcitriol treatment (15 micrograms/g ointment), the staining pattern for CDw49c, CDw49f and CD29 was markedly changed in epidermis of lesional psoriatic skin, reverting to the staining pattern characteristic for the nonlesional psoriatic or normal human skin, although epidermal expression of CDw49f was still upregulated and CDw49e-, CDw49f-, CD29-, and CD44(std.)-immunoreactive inflammatory and endothelial cells were still to be found in the dermal compartment.
Reichrath
J
J
Vitamin D, Skin, and Bone Research Laboratory, Boston University Medical Center, MA, USA.
Horf
R
R
Chen
T C
TC
Müller
S M
SM
Sanan
D
D
Holick
M F
MF
D000287:Administration, Topical; D015703:Antigens, CD / Q000378:metabolism; D001706:Biopsy; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D039421:Integrin alpha2; D039422:Integrin alpha3; D039482:Integrin alpha5; D039503:Integrin alpha6; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000187:drug effects / Q000378:metabolism*; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism
D015703:Antigens, CD; D018960:Hyaluronan Receptors; D039421:Integrin alpha2; D039422:Integrin alpha3; D039482:Integrin alpha5; D039503:Integrin alpha6; D019012:Integrin beta1; D016023:Integrins; D002117:Calcitriol