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The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria.

Silva-García O, Valdez-Alarcón JJ, Baizabal-Aguirre VM - Mediators Inflamm. (2014)

Bottom Line: During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation.The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury.Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections.

View Article: PubMed Central - PubMed

Affiliation: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km. 9.5 s/n Carretera Morelia-Zinapécuaro, La Palma, Tarímbaro, 58893 Morelia, MICH, Mexico.

ABSTRACT
Innate immunity against pathogenic bacteria is critical to protect host cells from invasion and infection as well as to develop an appropriate adaptive immune response. During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation. The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury. Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections. Our main goal in this review is to discuss the mechanism used by several pathogenic bacteria to modulate the inflammatory response through the Wnt/β-catenin signaling pathway. We think that a deep insight into the role of Wnt/β-catenin signaling in the inflammation may open new venues for biotechnological approaches designed to control bacterial infectious diseases.

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Related in: MedlinePlus

The PI3K/Akt signaling pathway enhances β-catenin activation. In colon epithelial cells infected with Citrobacter rodentium, Akt phosphorylates β-catenin at Ser552. The activation of β-catenin increases c-myc and reduces TNFα and IFNγ expression. An opposite effect is observed in cells incubated with the PI3K inhibitor LY294002.
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fig3: The PI3K/Akt signaling pathway enhances β-catenin activation. In colon epithelial cells infected with Citrobacter rodentium, Akt phosphorylates β-catenin at Ser552. The activation of β-catenin increases c-myc and reduces TNFα and IFNγ expression. An opposite effect is observed in cells incubated with the PI3K inhibitor LY294002.

Mentions: GSK3β is a downstream effector of the phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway as well as the Wnt/β-catenin destruction complex that negatively regulates β-catenin. The ability of GSK3β to promote or suppress the inflammatory response depends on the cell type and the stimulus [19]. In C. rodentium infections of CEC, Akt inhibits GSK3β by phosphorylation at Ser9 [20] with no phenotypic consequence reported so far. It is still not known yet whether this GSK3β phosphorylation depends on Fzd or TLR activation. Despite this lack of information, it is recognized that activation of the PI3K/Akt and Wnt/β-catenin pathways may cooperate to enhance β-catenin activity in C. rodentium infection mice models (Figure 3). In this context, it is also important to mention that in CEC infected with the Phopc Salmonella strain, AvrA enhanced β-catenin phosphorylation at Ser552 by increasing Akt expression and Akt phosphorylation at Thr308 [21]. This evidence suggests that the PI3K/Akt signaling pathway cooperates to increase β-catenin activity in Phopc Salmonella infections. However, whether AvrA directly alters PI3K activity, which is upstream of Akt, is not known. Future experiments should be designed to identify C. rodentium effector proteins responsible for β-catenin activation, which is also associated with CEC hyperplasia [20].


The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria.

Silva-García O, Valdez-Alarcón JJ, Baizabal-Aguirre VM - Mediators Inflamm. (2014)

The PI3K/Akt signaling pathway enhances β-catenin activation. In colon epithelial cells infected with Citrobacter rodentium, Akt phosphorylates β-catenin at Ser552. The activation of β-catenin increases c-myc and reduces TNFα and IFNγ expression. An opposite effect is observed in cells incubated with the PI3K inhibitor LY294002.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127235&req=5

fig3: The PI3K/Akt signaling pathway enhances β-catenin activation. In colon epithelial cells infected with Citrobacter rodentium, Akt phosphorylates β-catenin at Ser552. The activation of β-catenin increases c-myc and reduces TNFα and IFNγ expression. An opposite effect is observed in cells incubated with the PI3K inhibitor LY294002.
Mentions: GSK3β is a downstream effector of the phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway as well as the Wnt/β-catenin destruction complex that negatively regulates β-catenin. The ability of GSK3β to promote or suppress the inflammatory response depends on the cell type and the stimulus [19]. In C. rodentium infections of CEC, Akt inhibits GSK3β by phosphorylation at Ser9 [20] with no phenotypic consequence reported so far. It is still not known yet whether this GSK3β phosphorylation depends on Fzd or TLR activation. Despite this lack of information, it is recognized that activation of the PI3K/Akt and Wnt/β-catenin pathways may cooperate to enhance β-catenin activity in C. rodentium infection mice models (Figure 3). In this context, it is also important to mention that in CEC infected with the Phopc Salmonella strain, AvrA enhanced β-catenin phosphorylation at Ser552 by increasing Akt expression and Akt phosphorylation at Thr308 [21]. This evidence suggests that the PI3K/Akt signaling pathway cooperates to increase β-catenin activity in Phopc Salmonella infections. However, whether AvrA directly alters PI3K activity, which is upstream of Akt, is not known. Future experiments should be designed to identify C. rodentium effector proteins responsible for β-catenin activation, which is also associated with CEC hyperplasia [20].

Bottom Line: During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation.The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury.Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections.

View Article: PubMed Central - PubMed

Affiliation: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km. 9.5 s/n Carretera Morelia-Zinapécuaro, La Palma, Tarímbaro, 58893 Morelia, MICH, Mexico.

ABSTRACT
Innate immunity against pathogenic bacteria is critical to protect host cells from invasion and infection as well as to develop an appropriate adaptive immune response. During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation. The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury. Among the many signaling pathways activated, the canonical Wnt/β-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections. Our main goal in this review is to discuss the mechanism used by several pathogenic bacteria to modulate the inflammatory response through the Wnt/β-catenin signaling pathway. We think that a deep insight into the role of Wnt/β-catenin signaling in the inflammation may open new venues for biotechnological approaches designed to control bacterial infectious diseases.

Show MeSH
Related in: MedlinePlus