Abstract
TGF-βs are cytokines that signal through the receptor
complex of type I and type II receptors. Hemidesmosome (BP180, BP230,
plectin/HD1, α6β4 integrin), anchoring
filaments (laminin 5), and anchoring fibrils (collagen VII) form
a hemidesmosomal adhesion complex that provides stable adherence
of keratinocytes to the epidermal basement membrane. Nidogen, collagen
IV, and laminins are components of the basement membrane, integrins
are cell adhesion molecules, and tenascin-C is a matrix protein.
The expression of TGF-β receptors I and II was studied
in normal epidermis and lesional and non-lesional psoriatic epidermis
by immunohistochemistry. TGF-β1 and TGF-β2 in
suction blister fluid and serum were determined by enzyme-linked
immunoassay. Suction blister fluid and serum samples were obtained
from acne patients before and after oral isotretinoin treatment.
Suction blister fluid samples were also obtained from healthy volunteers
in two age groups from a control site and a betamethasone-pretreated
site. The expression of BP180, BP230, plectin/HD1, α6
integrin, β4 integrin, laminin 5, collagen VII, collagen
IV, nidogen, laminin α3 chain, and laminin β1g1
chains was studied in uninvolved dermatitis herpetiformis skin by
the immunofluorescence technique. The ultrastructure of the hemidesmosomal
inner plaque was studied in uninvolved dermatitis herpetiformis
skin by electron microscopy. The suction blister method was used
to study intact blisters, open wounds (=blister roofs removed
right after blister induction) and calcipotriol-pretreated open
wounds in healthy volunteers. The reepithelialization rate and the
expression of BP180, BP230, plectin/HD1, β4 integrin,
laminin 5, collagen VII, laminin α5 chain, laminin β1
chain, tenascin-C, αvβ5 integrin, β5
integrin, α5 integrin, and α9 integrin during
reepithelialization were studied by haematoxylin and eosin stainings
and the immunofluorescence technique. BP180, BP230, and plectin/HD1
expression were analyzed by body site to exclude regional variation.
In normal epidermis, TGF-β receptors I and II were
detected in the basal epidermis. Diffusion calculations suggest
that circulation is likely to be a major source of TGF-β for
TGF-β receptors in the basal epidermis. Downregulation
of TGF-β receptors I and II was seen in lesional psoriatic epidermis,
suggesting that hyperproliferating lesional epidermis may have lost
TGF-β-mediated growth inhibition. Isotretinoin did not
affect the serum TGF-β1 or TGF-β2 levels, but
caused a 19% local increase in suction blister fluid TGF-β1.
Betamethasone caused a 17% decrease in suction blister
fluid TGF-β1, presumably due to glucocorticoid-induced
vasoconstriction. Modulation of the interstitial fluid TGF-β1
concentration may be one mechanism by which isotretinoin and betamethasone
mediate their effects in skin. Immunoreactivity for BP230 and plectin/HD1
was decreased in the basement membrane zone in uninvolved dermatitis
herpetiformis skin in a significant proportion of the patients,
suggesting distinct molecular changes in BP230 and plectin/HD1.
This may be a factor contributing to blister formation. Reepithelialization
rate was considerably slower in intact blisters than in open wounds
and was not affected by calcipotriol. BP230 and plectin/HD1 appeared
earlier in intact blisters than in open wounds. Reepithelialization
took place on a continuous laminin sheath in intact blisters, but
the laminin sheath in open wounds was partially discontinuous. It
was a novel finding that integrin αvβ5 and integrin β5
antibodies showed divergent distributions in regenerating epidermis.
The present results suggest that, in some bullous diseases, removal
of the blister roof could accelerate blister healing, calcipotriol
treatment does not delay wound epithelialization, a continuous laminin
sheath may inhibit reepithelialization, and the formation of the hemidesmosomal
inner plaque at the leading edge takes place earlier in the more
slowly reepithelializing intact blisters than in open wounds.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5712-X |
| Date | 10 July 2000 |
| Creators | Leivo, T. (Tomi) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2000 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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