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 |
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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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