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The Mycoplasma hyorhinis p37 Protein Rapidly Induces Genes in Fibroblasts Associated with Inflammation and Cancer.

Gomersall AC, Phan HA, Iacuone S, Li SF, Parish RW - PLoS ONE (2015)

Bottom Line: The p37 protein at the surface of Mycoplasma hyorhinis cells forms part of a high-affinity transport system and has been found associated with animal and human cancers.This gene activation was principally via the Tlr4 receptor.Blocking the IL6 receptor or inhibiting STAT3 signalling resulted in increased p37-induced gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal, Plant and Soil Science, AgriBio, La Trobe University, Melbourne, Victoria, Australia.

ABSTRACT
The p37 protein at the surface of Mycoplasma hyorhinis cells forms part of a high-affinity transport system and has been found associated with animal and human cancers. Here we show in NIH3T3 fibroblasts, p37 rapidly induces the expression of genes implicated in inflammation and cancer progression. This gene activation was principally via the Tlr4 receptor. Activity was lost from p37 when the C-terminal 20 amino acids were removed or the four amino acids specific for the hydrogen bonding of thiamine pyrophosphate had been replaced by valine. Blocking the IL6 receptor or inhibiting STAT3 signalling resulted in increased p37-induced gene expression. Since cancer associated fibroblasts support growth, invasion and metastasis via their ability to regulate tumour-related inflammation, the rapid induction in fibroblasts of pro-inflammatory genes by p37 might be expected to influence cancer development.

No MeSH data available.


Related in: MedlinePlus

IL6R inhibition effect on p37-induced gene expression in NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with 25 μg ml-1 p37 for 24 hours (black) or pre-treated with 0.1 μg ml-1 IL6Ri for an hour prior to 25 μg ml-1 p37 treatment for 24 hours (grey). Significant differences between p37 + IL6Ri treatment and p37 treatment was calculated using ANOVA analysis (+p<0.05, ++p<0.01, +++p<0.001).
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pone.0140753.g005: IL6R inhibition effect on p37-induced gene expression in NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with 25 μg ml-1 p37 for 24 hours (black) or pre-treated with 0.1 μg ml-1 IL6Ri for an hour prior to 25 μg ml-1 p37 treatment for 24 hours (grey). Significant differences between p37 + IL6Ri treatment and p37 treatment was calculated using ANOVA analysis (+p<0.05, ++p<0.01, +++p<0.001).

Mentions: NIH3T3 fibroblasts possess the IL6 receptor (IL6R) [32]. Cells were incubated with the IL6 receptor-α chain specific monoclonal antibody (IL6Ri) which is directed against mouse/rat interleukin 6 receptor (IL6R) and its soluble counterpart (sIL6R). The antibody blocks IL6 binding to the gp130 receptor. When IL6Ri (0.1 μg ml-1) was added with p37 (25 μg ml-1) to NIH3T3 fibroblasts, expression of ten of the fifteen genes tested was significantly higher than in p37 treated controls (Fig 5). The genes most strongly activated were FK506 binding protein 5 (Fkbp5; 56-fold greater than the p37-treated control), Hp (19-fold), Lumican (Lum; 16-fold), C3 (10-fold), IL6 (9-fold), Lcn2 (8-fold) and Dcn (6-fold). Saa3 expression was decreased by 60%. However, IL6 and Dcn expression were increased 6-fold by IL6Ri treatment alone (S8B Fig).


The Mycoplasma hyorhinis p37 Protein Rapidly Induces Genes in Fibroblasts Associated with Inflammation and Cancer.

Gomersall AC, Phan HA, Iacuone S, Li SF, Parish RW - PLoS ONE (2015)

IL6R inhibition effect on p37-induced gene expression in NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with 25 μg ml-1 p37 for 24 hours (black) or pre-treated with 0.1 μg ml-1 IL6Ri for an hour prior to 25 μg ml-1 p37 treatment for 24 hours (grey). Significant differences between p37 + IL6Ri treatment and p37 treatment was calculated using ANOVA analysis (+p<0.05, ++p<0.01, +++p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4626034&req=5

pone.0140753.g005: IL6R inhibition effect on p37-induced gene expression in NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with 25 μg ml-1 p37 for 24 hours (black) or pre-treated with 0.1 μg ml-1 IL6Ri for an hour prior to 25 μg ml-1 p37 treatment for 24 hours (grey). Significant differences between p37 + IL6Ri treatment and p37 treatment was calculated using ANOVA analysis (+p<0.05, ++p<0.01, +++p<0.001).
Mentions: NIH3T3 fibroblasts possess the IL6 receptor (IL6R) [32]. Cells were incubated with the IL6 receptor-α chain specific monoclonal antibody (IL6Ri) which is directed against mouse/rat interleukin 6 receptor (IL6R) and its soluble counterpart (sIL6R). The antibody blocks IL6 binding to the gp130 receptor. When IL6Ri (0.1 μg ml-1) was added with p37 (25 μg ml-1) to NIH3T3 fibroblasts, expression of ten of the fifteen genes tested was significantly higher than in p37 treated controls (Fig 5). The genes most strongly activated were FK506 binding protein 5 (Fkbp5; 56-fold greater than the p37-treated control), Hp (19-fold), Lumican (Lum; 16-fold), C3 (10-fold), IL6 (9-fold), Lcn2 (8-fold) and Dcn (6-fold). Saa3 expression was decreased by 60%. However, IL6 and Dcn expression were increased 6-fold by IL6Ri treatment alone (S8B Fig).

Bottom Line: The p37 protein at the surface of Mycoplasma hyorhinis cells forms part of a high-affinity transport system and has been found associated with animal and human cancers.This gene activation was principally via the Tlr4 receptor.Blocking the IL6 receptor or inhibiting STAT3 signalling resulted in increased p37-induced gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal, Plant and Soil Science, AgriBio, La Trobe University, Melbourne, Victoria, Australia.

ABSTRACT
The p37 protein at the surface of Mycoplasma hyorhinis cells forms part of a high-affinity transport system and has been found associated with animal and human cancers. Here we show in NIH3T3 fibroblasts, p37 rapidly induces the expression of genes implicated in inflammation and cancer progression. This gene activation was principally via the Tlr4 receptor. Activity was lost from p37 when the C-terminal 20 amino acids were removed or the four amino acids specific for the hydrogen bonding of thiamine pyrophosphate had been replaced by valine. Blocking the IL6 receptor or inhibiting STAT3 signalling resulted in increased p37-induced gene expression. Since cancer associated fibroblasts support growth, invasion and metastasis via their ability to regulate tumour-related inflammation, the rapid induction in fibroblasts of pro-inflammatory genes by p37 might be expected to influence cancer development.

No MeSH data available.


Related in: MedlinePlus