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Urokinase plasminogen activator mRNA is induced by IL‐1α and TNF‐α in in vitro acantholysis
Author(s) -
Feliciani Claudio,
Toto Paola,
Wang Binghe,
Sauder Daniel N.,
Amerio Pierluigi,
Tulli Antonio
Publication year - 2003
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1034/j.1600-0625.2002.120415.x
Subject(s) - acantholysis , plasminogen activator , tumor necrosis factor alpha , plasmin , urokinase , cytokine , keratinocyte , messenger rna , biology , microbiology and biotechnology , interleukin 8 , antibody , endocrinology , in vitro , immunology , medicine , biochemistry , enzyme , autoantibody , gene
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‐1α, anti‐TNF‐α 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.