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Analysis of the signal transduction pathway of nickel‐induced matrix metalloproteinase‐2 expression in the human keratinocytes in vitro : preliminary findings
Author(s) -
Perfetto Brunella,
Lamberti Monica,
Giuliano Maria Teresa,
Canozo Nunzia,
Cammarota Marcella,
Baroni Adone
Publication year - 2007
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/j.1600-0560.2006.00647.x
Subject(s) - hacat , calphostin c , signal transduction , protein kinase c , microbiology and biotechnology , chemistry , protein kinase a , activator (genetics) , matrix metalloproteinase , cancer research , kinase , biology , biochemistry , in vitro , gene
Background: Nickel can induce cellular and nuclear damages responsible for chronic diseases, like allergic contact dermatitis (ACD). We previously showed that matrix metalloproteinase‐2 (MMP‐2) gene expression was induced by nickel in nontumorigenic human keratinocytes cell line (HaCat). Objective: To investigate the signal transduction pathways involved in gelatinolytic activity induced in HaCat under nickel stimulation. Methods: We analyzed the involvement of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (PTK), nuclear factor‐kB (NF‐kB) and activator protein‐1 (AP‐1) using specific inhibitors (H89, calphostin C, genistein, carpain and curcumin) by electrophoretic mobility shift assay, reverse transcription‐polymerase chain reaction and gelatin zymography. Results: Our results indicate that nickel‐induced MMP‐2 production was inhibited with PTK, PKC and AP‐1 specific inhibitors. Moreover, both PKA and NF‐kB were not involved in nickel pathway. Conclusions: Using HaCat, we showed that curcumin and genistein can revert nickel‐induced MMP‐2 upregulation. Whether the use of PTK and AP‐1 inhibitors has therapeutic ramifications in the management of ACD remains to be investigated.