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Association of self-DNA mediated TLR9-related gene-, DNA methyltransferase and cytokeratin protein expression alterations in HT29-cells to DNA fragment length and methylation status

Fűri, István and Sipos, Ferenc and Spisák, Sándor and Kiszner, Gergő and Wichmann, Barnabás and Schöller, Andrea and Tulassay, Zsolt and Műzes, Györgyi and Molnár, Béla (2013) Association of self-DNA mediated TLR9-related gene-, DNA methyltransferase and cytokeratin protein expression alterations in HT29-cells to DNA fragment length and methylation status. THE SCIENTIFIC WORLD JOURNAL. No.-293296. ISSN 1537-744X

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Abstract

To understand the biologic role of self-DNA bound to Toll-like Receptor 9 (TLR9), we assayed its effect on gene and methyltransferase expressions and cell differentiation in HT29 cells. HT29 cells were incubated separately with type-1 (normally methylated/nonfragmented), type-2 (normally methylated/fragmented), type-3 (hypermethylated/nonfragmented), or type-4 (hypermethylated/fragmented) self-DNAs. Expression levels of TLR9-signaling and proinflammatory cytokine-related genes were assayed by qRT-PCR. Methyltransferase activity and cell differentiation were examined by using DNA methyltransferase (DNMT1, -3A, -3B) and cytokeratin (CK) antibodies. Treatment with type-1 DNA resulted in significant increase in TLR9 expression. Type-2 treatment resulted in the overexpression of TLR9-related signaling molecules (MYD88A, TRAF6) and the IL8 gene. In the case of type-3 treatment, significant overexpression of NFkB, IRAK2, and IL8 as well as downregulation of TRAF6 was detected. Using type-4 DNA, TRAF6 and MYD88A gene expression was upregulated, while MYD88B, IRAK2, IL8, and TNFSF10 were all underexpressed. CK expression was significantly higher only after type-1 DNA treatment. DNMT3A expression could also be induced by type-1 DNA treatment. DNA structure may play a significant role in activation of the TLR9-dependent and even independent proinflammatory pathways. There may be a molecular link between TLR9 signaling and DNMT3A. The mode of self-DNA treatment may influence HT29 cell differentiation.

Item Type: Article
Additional Information: Fűri I. és Sipos F. társ-elsőszerzők Műzes Gy. és Molnár B. társ-utolsószerzők
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 06 Feb 2014 03:28
Last Modified: 06 Feb 2014 03:28
URI: http://real.mtak.hu/id/eprint/9895

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