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Gene expression regulation in retinal pigment epithelial cells induced by viral RNA and viral/bacterial DNA.

Brosig A, Kuhrt H, Wiedemann P, Kohen L, Bringmann A, Hollborn M - Mol. Vis. (2015)

Bottom Line: We compared the effects of synthetic viral RNA (poly(I:C)) and viral/bacterial DNA (CpG-ODN) on the expression of genes known to be involved in the development of AMD in retinal pigment epithelial (RPE) cells.The widespread effects of viral RNA, and the restricted effects of viral/bacterial DNA, on the gene expression pattern of RPE cells may suggest that viral RNA rather than viral/bacterial DNA induces physiologic alterations of RPE cells, which may aggravate inflammation in the aged retina.The data also suggest that selective inhibition of distinct signal transduction pathways or individual transcription factors may not be effective to inhibit viral retinal inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany.

ABSTRACT

Purpose: The pathogenesis of age-related macular degeneration (AMD) is associated with systemic and local inflammation. Various studies suggested that viral or bacterial infection may aggravate retinal inflammation in the aged retina. We compared the effects of synthetic viral RNA (poly(I:C)) and viral/bacterial DNA (CpG-ODN) on the expression of genes known to be involved in the development of AMD in retinal pigment epithelial (RPE) cells.

Methods: Cultured human RPE cells were stimulated with poly(I:C; 500 µg/ml) or CpG-ODN (500 nM). Alterations in gene expression and protein secretion were determined with real-time RT-PCR and ELISA, respectively. Phosphorylation of signal transduction molecules was revealed by western blotting.

Results: Poly(I:C) induced gene expression of the pattern recognition receptor TLR3, transcription factors (HIF-1α, p65/NF-κB), the angiogenic factor bFGF, inflammatory factors (IL-1β, IL-6, TNFα, MCP-1, MIP-2), and complement factors (C5, C9, CFB). Poly(I:C) also induced phosphorylation of ERK1/2 and p38 MAPK proteins, and the secretion of bFGF and TNFα from the cells. CpG-ODN induced moderate gene expression of transcription factors (p65/NF-κB, NFAT5) and complement factors (C5, C9), while it had no effect on the expression of various TLR, angiogenic factor, and inflammatory factor genes. The activities of various signal transduction pathways and transcription factors were differentially involved in mediating the poly(I:C)-induced transcriptional activation of distinct genes.

Conclusions: The widespread effects of viral RNA, and the restricted effects of viral/bacterial DNA, on the gene expression pattern of RPE cells may suggest that viral RNA rather than viral/bacterial DNA induces physiologic alterations of RPE cells, which may aggravate inflammation in the aged retina. The data also suggest that selective inhibition of distinct signal transduction pathways or individual transcription factors may not be effective to inhibit viral retinal inflammation.

No MeSH data available.


Related in: MedlinePlus

Schematic summary of the effects of viral dsRNA on the gene expression of cultured human RPE cells. Activation of the pattern recognition receptor TLR3 by dsRNA results in activation of various signal transduction pathways (e.g., ERK1/2, p38 MAPK, JNK, PI3K-Akt) which are differentially involved in inducing the gene expression of TLR3, inflammatory factors such as TNFα and IL-1β, complement factors such as CFB, and the angiogenic factor bFGF. The expression of various genes is differentially induced by the transcription factors HIF-1, NF-κB, and STAT3. In addition to gene expression induction, dsRNA induces the secretion of inflammatory (TNFα) and angiogenic factors (bFGF) from the cells. It remains to be determined whether dsRNA also induces a secretion of further proteins, such as CFB, IL-1β, and MCP-1.
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f10: Schematic summary of the effects of viral dsRNA on the gene expression of cultured human RPE cells. Activation of the pattern recognition receptor TLR3 by dsRNA results in activation of various signal transduction pathways (e.g., ERK1/2, p38 MAPK, JNK, PI3K-Akt) which are differentially involved in inducing the gene expression of TLR3, inflammatory factors such as TNFα and IL-1β, complement factors such as CFB, and the angiogenic factor bFGF. The expression of various genes is differentially induced by the transcription factors HIF-1, NF-κB, and STAT3. In addition to gene expression induction, dsRNA induces the secretion of inflammatory (TNFα) and angiogenic factors (bFGF) from the cells. It remains to be determined whether dsRNA also induces a secretion of further proteins, such as CFB, IL-1β, and MCP-1.

Mentions: Viral RNA induces the activation of RPE cells, as indicated by the increased phosphorylation levels of intracellular signal transduction molecules and elevated expression of distinct transcription factor genes (Figure 10). The activities of ERK1/2, p38 MAPK, JNK, and PI3K, and of various transcription factors, are differentially involved in mediating the poly(I:C)-induced transcriptional activation of distinct genes (Figure 10). The data suggest that selective inhibition of distinct intracellular signal transduction pathways or of individual transcription factors may not be effective to inhibit viral inflammation of the retina.


Gene expression regulation in retinal pigment epithelial cells induced by viral RNA and viral/bacterial DNA.

Brosig A, Kuhrt H, Wiedemann P, Kohen L, Bringmann A, Hollborn M - Mol. Vis. (2015)

Schematic summary of the effects of viral dsRNA on the gene expression of cultured human RPE cells. Activation of the pattern recognition receptor TLR3 by dsRNA results in activation of various signal transduction pathways (e.g., ERK1/2, p38 MAPK, JNK, PI3K-Akt) which are differentially involved in inducing the gene expression of TLR3, inflammatory factors such as TNFα and IL-1β, complement factors such as CFB, and the angiogenic factor bFGF. The expression of various genes is differentially induced by the transcription factors HIF-1, NF-κB, and STAT3. In addition to gene expression induction, dsRNA induces the secretion of inflammatory (TNFα) and angiogenic factors (bFGF) from the cells. It remains to be determined whether dsRNA also induces a secretion of further proteins, such as CFB, IL-1β, and MCP-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554413&req=5

f10: Schematic summary of the effects of viral dsRNA on the gene expression of cultured human RPE cells. Activation of the pattern recognition receptor TLR3 by dsRNA results in activation of various signal transduction pathways (e.g., ERK1/2, p38 MAPK, JNK, PI3K-Akt) which are differentially involved in inducing the gene expression of TLR3, inflammatory factors such as TNFα and IL-1β, complement factors such as CFB, and the angiogenic factor bFGF. The expression of various genes is differentially induced by the transcription factors HIF-1, NF-κB, and STAT3. In addition to gene expression induction, dsRNA induces the secretion of inflammatory (TNFα) and angiogenic factors (bFGF) from the cells. It remains to be determined whether dsRNA also induces a secretion of further proteins, such as CFB, IL-1β, and MCP-1.
Mentions: Viral RNA induces the activation of RPE cells, as indicated by the increased phosphorylation levels of intracellular signal transduction molecules and elevated expression of distinct transcription factor genes (Figure 10). The activities of ERK1/2, p38 MAPK, JNK, and PI3K, and of various transcription factors, are differentially involved in mediating the poly(I:C)-induced transcriptional activation of distinct genes (Figure 10). The data suggest that selective inhibition of distinct intracellular signal transduction pathways or of individual transcription factors may not be effective to inhibit viral inflammation of the retina.

Bottom Line: We compared the effects of synthetic viral RNA (poly(I:C)) and viral/bacterial DNA (CpG-ODN) on the expression of genes known to be involved in the development of AMD in retinal pigment epithelial (RPE) cells.The widespread effects of viral RNA, and the restricted effects of viral/bacterial DNA, on the gene expression pattern of RPE cells may suggest that viral RNA rather than viral/bacterial DNA induces physiologic alterations of RPE cells, which may aggravate inflammation in the aged retina.The data also suggest that selective inhibition of distinct signal transduction pathways or individual transcription factors may not be effective to inhibit viral retinal inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany.

ABSTRACT

Purpose: The pathogenesis of age-related macular degeneration (AMD) is associated with systemic and local inflammation. Various studies suggested that viral or bacterial infection may aggravate retinal inflammation in the aged retina. We compared the effects of synthetic viral RNA (poly(I:C)) and viral/bacterial DNA (CpG-ODN) on the expression of genes known to be involved in the development of AMD in retinal pigment epithelial (RPE) cells.

Methods: Cultured human RPE cells were stimulated with poly(I:C; 500 µg/ml) or CpG-ODN (500 nM). Alterations in gene expression and protein secretion were determined with real-time RT-PCR and ELISA, respectively. Phosphorylation of signal transduction molecules was revealed by western blotting.

Results: Poly(I:C) induced gene expression of the pattern recognition receptor TLR3, transcription factors (HIF-1α, p65/NF-κB), the angiogenic factor bFGF, inflammatory factors (IL-1β, IL-6, TNFα, MCP-1, MIP-2), and complement factors (C5, C9, CFB). Poly(I:C) also induced phosphorylation of ERK1/2 and p38 MAPK proteins, and the secretion of bFGF and TNFα from the cells. CpG-ODN induced moderate gene expression of transcription factors (p65/NF-κB, NFAT5) and complement factors (C5, C9), while it had no effect on the expression of various TLR, angiogenic factor, and inflammatory factor genes. The activities of various signal transduction pathways and transcription factors were differentially involved in mediating the poly(I:C)-induced transcriptional activation of distinct genes.

Conclusions: The widespread effects of viral RNA, and the restricted effects of viral/bacterial DNA, on the gene expression pattern of RPE cells may suggest that viral RNA rather than viral/bacterial DNA induces physiologic alterations of RPE cells, which may aggravate inflammation in the aged retina. The data also suggest that selective inhibition of distinct signal transduction pathways or individual transcription factors may not be effective to inhibit viral retinal inflammation.

No MeSH data available.


Related in: MedlinePlus