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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20 amino acids were removed or the four amino acids specific for the hydrogen bonding of thiamine pyrophosphate had been replaced by valine.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

Mutant p37 affect on gene expression of NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with either 25 μg ml-1 p37 with a mutated TPP binding site (grey) or native p37 (black) for 24 hours. Significant differences between mutant p37 and native p37 treatments were calculated using ANOVA analysis (+p<0.05, ++ p<0.01, +++p<0.001).
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pone.0140753.g004: Mutant p37 affect on gene expression of NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with either 25 μg ml-1 p37 with a mutated TPP binding site (grey) or native p37 (black) for 24 hours. Significant differences between mutant p37 and native p37 treatments were calculated using ANOVA analysis (+p<0.05, ++ p<0.01, +++p<0.001).

Mentions: The crystalline structure of p37 has been defined to 1.9 Å resolution [29]. P37 is an alpha/beta class protein consisting of two domains separated by a cleft which modelling indicates binds thiamine pyrophosphate (TPP). The four amino acids S255, F256, S257 and K258 are specific to the hydrogen bonding of TPP. Site-directed mutagenesis was used to replace each of these four amino acids with valine. Mutant p37 upregulated Angptl4, C3, Lcn2 and Saa3 but to much lower levels than native p37 (Fig 4). However, the level of LIF expression was 3-fold higher with mutant p37 than with native p37.


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)

Mutant p37 affect on gene expression of NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with either 25 μg ml-1 p37 with a mutated TPP binding site (grey) or native p37 (black) for 24 hours. Significant differences between mutant p37 and native p37 treatments were calculated using ANOVA analysis (+p<0.05, ++ p<0.01, +++p<0.001).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4626034&req=5

pone.0140753.g004: Mutant p37 affect on gene expression of NIH3T3 fibroblasts.Quantitative PCR analysis of NIH3T3 fibroblasts treated with either 25 μg ml-1 p37 with a mutated TPP binding site (grey) or native p37 (black) for 24 hours. Significant differences between mutant p37 and native p37 treatments were calculated using ANOVA analysis (+p<0.05, ++ p<0.01, +++p<0.001).
Mentions: The crystalline structure of p37 has been defined to 1.9 Å resolution [29]. P37 is an alpha/beta class protein consisting of two domains separated by a cleft which modelling indicates binds thiamine pyrophosphate (TPP). The four amino acids S255, F256, S257 and K258 are specific to the hydrogen bonding of TPP. Site-directed mutagenesis was used to replace each of these four amino acids with valine. Mutant p37 upregulated Angptl4, C3, Lcn2 and Saa3 but to much lower levels than native p37 (Fig 4). However, the level of LIF expression was 3-fold higher with mutant p37 than with native p37.

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