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Induction of matrix metalloproteinase‐9 (MMP‐9) in lipopolysaccharide‐stimulated primary astrocytes is mediated by extracellular signal‐regulated protein kinase 1/2 (Erk1/2)
Author(s) -
Lee Woo Jong,
Shin Chan Young,
Yoo Byoung Kwon,
Ryu Jae Ryun,
Choi Eui Yul,
Cheong Jae Hoon,
Ryu Jong Hoon,
Ko Kwang Ho
Publication year - 2003
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10131
Subject(s) - protein kinase c , mapk/erk pathway , biology , kinase , protein kinase a , microbiology and biotechnology , signal transduction , lipopolysaccharide , matrix metalloproteinase , neuroglia , astrocyte , endocrinology , biochemistry , central nervous system
In the present study, we investigated whether the activation of protein kinase C (PKC) and extracellular signal‐regulated kinase 1/2 (Erk1/2) are involved in the induction of MMP‐9 in lipopolysaccharide (LPS)–stimulated primary astrocytes. The expression of MMP‐9 but not MMP‐2 was increased by LPS. LPS treatment induced activation of Erk1/2 within 30 min, which was dose‐dependently inhibited by PD98059, a specific inhibitor of the Erk kinase (MEK). In this condition, PD98059 blocked the increase in MMP‐9 protein and mRNA level as well as gelatin‐digesting activity. Inhibition of PKC activity blocked the LPS‐induced activation of Erk1/2 as well as MMP‐9 expression. In addition, activation of PKC by phorbol myristoyl acetate (PMA) activated Erk1/2 with concomitant increase in MMP‐9 production. Moreover, treatment of PD98059 dose‐dependently decreased the PMA‐induced MMP‐9 expression. The results from the present study suggest that induction of MMP‐9 by LPS in rat primary astrocytes is mediated, at least in part, by the sequential activation of PKC and Erk1/2. The Erk1/2‐mediated MMP‐9 induction may provide insights into the regulation of MMP‐9 production in CNS, which may occur in vivo in pathological situations such as CNS inflammation. GLIA 41:15–24, 2003. © 2003 Wiley‐Liss, Inc.