The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1α and TNF-α are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1α and TNF-α are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1α, TNF-α and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1α, TNF-α and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1α/TNF-α mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1α, TNF-α and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-la, anti-TNF-a and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1α and anti-TNF-α antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1α/TNF-α mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1α/TNF-α in uPA induction. © Blackwell Munksgaard, 2003.

Urokinase plasminogen activator mRNA is induced by IL-1α and TNF-α in in vitro acantholysis / Feliciani, C.; a and Toto, C.; a and Wang, P.; c and Sauder, B.; c and Amerio, D. N.; b and Tulli, P.; A, A.. - In: EXPERIMENTAL DERMATOLOGY. - ISSN 0906-6705. - 12:4(2003), pp. 466-471. [10.1034/j.1600-0625.2002.120415.x]

Urokinase plasminogen activator mRNA is induced by IL-1α and TNF-α in in vitro acantholysis

c. Feliciani
Writing – Original Draft Preparation
;
2003

Abstract

The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1α and TNF-α are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1α and TNF-α are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1α, TNF-α and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1α, TNF-α and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1α/TNF-α mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1α, TNF-α and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-la, anti-TNF-a and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1α and anti-TNF-α antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1α/TNF-α mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1α/TNF-α in uPA induction. © Blackwell Munksgaard, 2003.
Urokinase plasminogen activator mRNA is induced by IL-1α and TNF-α in in vitro acantholysis / Feliciani, C.; a and Toto, C.; a and Wang, P.; c and Sauder, B.; c and Amerio, D. N.; b and Tulli, P.; A, A.. - In: EXPERIMENTAL DERMATOLOGY. - ISSN 0906-6705. - 12:4(2003), pp. 466-471. [10.1034/j.1600-0625.2002.120415.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2866480
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