Modulation in vitro of keratinocyte integrins by interferon-alpha and interferon-gamma.
BACKGROUND
Interferon-alpha and -gamma are glycoproteins with antiviral and immunoregulatory properties. In vitro studies have shown a role for these cytokines in the regulation of epidermal keratinocyte growth and differentiation. In the same way, integrins are adhesion molecules which regulate keratinocyte proliferation and differentiation.


OBJECTIVE
To determine whether the regulatory activity of interferons on keratinocyte proliferation and differentiation is related to a modulation of keratinocyte integrins.


METHODS
Two different methods were used: monolayers and reconstituted skin, incubated either with 1,200 U/mL interferon-alpha or 500 U/mL interferon-gamma or control medium for 48 h. The integrin expression was assessed by flow cytometry and immunohistochemistry.


RESULTS
In monolayers, only the alpha3 subunit was significantly inhibited by interferon-gamma. In reconstituted skin, where keratinocytes are differentiated, both interferons had an inductive effect on beta1 expression and interferon-alpha had an inhibitory effect on alpha6 expression.


CONCLUSIONS
Interferon-alpha and -gamma induce a modulatory effect on alpha3, alpha6 and beta1 which appears to be related to the state of differentiation. Moreover, the decreased expression of alpha6 and alpha3 could be one of the mechanisms involved in the formation of bullous lesions during long-term interferon therapy.
Tenaud
Isabelle
I
Laboratory of Immuno-Dermatology, INSERM U463, Nantes, France.
Leroy
Sabine
S
Chebassier
Nathalie
N
Dreno
Brigitte
B
D016525:Antigenic Modulation / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D066298:In Vitro Techniques; D038982:Integrin alpha2beta1 / Q000032:analysis / Q000187:drug effects; D039201:Integrin alpha3beta1 / Q000032:analysis / Q000187:drug effects; D039081:Integrin alpha5beta1 / Q000032:analysis / Q000187:drug effects; D039161:Integrin alpha6beta4 / Q000032:analysis / Q000187:drug effects; D016023:Integrins / Q000032:analysis* / Q000187:drug effects*; D016898:Interferon-alpha / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D019030:Receptors, Vitronectin / Q000032:analysis / Q000187:drug effects; D013997:Time Factors
D007155:Immunologic Factors; D038982:Integrin alpha2beta1; D039201:Integrin alpha3beta1; D039081:Integrin alpha5beta1; D039161:Integrin alpha6beta4; D016023:Integrins; D016898:Interferon-alpha; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5