RGD Reference Report - Lipoteichoic acid induces matrix metalloproteinase-9 expression via transactivation of PDGF receptors and NF-kappaB activation in rat brain astrocytes. - Rat Genome Database

RGD Reference Report - Lipoteichoic acid induces matrix metalloproteinase-9 expression via transactivation of PDGF receptors and NF-kappaB activation in rat brain astrocytes. - Rat Genome Database

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Lipoteichoic acid induces matrix metalloproteinase-9 expression via transactivation of PDGF receptors and NF-kappaB activation in rat brain astrocytes.
Authors:	Hsieh, HL Wang, HH Wu, CY Tung, WH Yang, CM
Citation:	Hsieh HL, etal., Neurotox Res. 2010 May;17(4):344-59. Epub 2009 Sep 10.
RGD ID:	2325160
Pubmed:	PMID:19763735 (View Abstract at PubMed)
DOI:	DOI:10.1007/s12640-009-9111-4 (Journal Full-text)
Bacterial infections have been shown to be involved in several inflammatory diseases such as brain inflammation. A major factor for these findings is due to the secretion of pro-inflammatory mediators by host cells triggered by the components released from the bacteria. Among these components, lipoteichoic acid (LTA), a component of Gram-positive bacterial cell wall, has been found to be elevated in cerebrospinal fluid of patients suffering from meningitis. Moreover, increased plasma levels of matrix metalloproteinases (MMPs), in particular MMP-9, have been observed in patients with brain inflammatory diseases and may contribute to disease pathology. However, the molecular mechanisms underlying LTA-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) remain poorly defined. Here, the data with zymographic, Western blotting, RT-PCR, and immunofluorescent staining analyses showed that LTA induced MMP-9 expression and activation via a TLR2-activated c-Src-dependent transactivation of PDGFR pathway. Transactivation of PDGFR led to activation of PI3K/Akt and p42/p44 MAPK and then activated the IKK/NF-kappaB cascade. The activated-NF-kappaB translocated into nucleus which bound to kappaB-binding site of MMP-9 promoter, and thereby turned on transcription of MMP-9. Eventually, upregulation of MMP-9 by LTA enhanced cell migration of astrocytes. Taken together, these results suggested that in RBA-1 cells, activation of NF-kappaB by a c-Src-dependent PI3K/Akt-p42/p44 MAPK activation mediated through transactivation of PDGFR is essential for MMP-9 gene upregulation induced by LTA. Understanding the regulation of MMP-9 expression and functional changes by LTA/TLR system on astrocytes may provide potential therapeutic targets of Gram-positive bacterial infection in brain disorders.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Src	Rat	positive regulation of gene expression		IMP		MMP-9	RGD

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Genes (Rattus norvegicus)

Src (SRC proto-oncogene, non-receptor tyrosine kinase)

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