Premium
Activation of toll‐like receptor‐9 induces matrix metalloproteinase‐9 expression through Akt and tumor necrosis factor‐α signaling
Author(s) -
Lim Eun-Jung,
Lee Sun-Hye,
Lee Jin-Gu,
Chin Byung-Ro,
Bae Yoe-Sik,
Kim Jae-Ryong,
Lee Chu-Hee,
Baek Suk-Hwan
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.06.100
Subject(s) - tlr9 , tumor necrosis factor alpha , protein kinase b , cpg oligodeoxynucleotide , pi3k/akt/mtor pathway , toll like receptor , chemistry , cpg site , matrix metalloproteinase , cancer research , phosphorylation , microbiology and biotechnology , receptor , signal transduction , biology , immunology , innate immune system , gene expression , biochemistry , dna methylation , gene
CpG oligodeoxunucleotide (ODN) plays an important role in immune cell function. The present study examined whether temporal control of toll‐like receptor (TLR)‐9 by CpG ODN can regulate the expression of matrix metalloproteinase‐9 (MMP‐9). CpG ODN induced the release of tumor necrosis factor (TNF)‐α and the expression of TNF receptor (TNFR)‐II, but not of TNFR‐I, in a time‐dependent manner and stimulated significant, though delayed, MMP‐9 expression. The endosomal acidification inhibitors, chloroquine or bafilomycin A, inhibited CpG ODN‐induced TNF‐α, TNFR‐II, and MMP‐9 expression. CpG ODN induced the phosphorylation of Akt, and the inhibition of Akt by LY294002 suppressed CpG ODN‐induced TNF‐α, TNFR‐II, and MMP‐9 expressions. Moreover, neutralizing TNF‐α antibody significantly suppressed CpG ODN‐induced MMP‐9 expression, suggesting the involvement of TNF‐α. These observations suggest that CpG ODN may play important roles in macrophage activation by regulating the expression of MMP‐9 via a TLR‐9/Akt/TNF‐α‐dependent signaling pathway.