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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

β-Catenin is an antagonist of the NF-κB pathway. In colon epithelial cells, Salmonella induces IL-8, TNFα, and Wnt expression via NF-κB activation. Moreover, the Salmonella typhimurium deubiquinating effector AvrA stabilizes IκBα and β-catenin. This step enhances β-catenin activity and at the same time inhibits NF-κB by stabilizing its inhibitor. The expression of Wnt in the first stage of infection stimulates Wnt/β-catenin pathway. The stabilized β-catenin then interacts with the NF-κB p50 subunit, decreasing its transcriptional activity. While NF-κB activity is inflammatory, its inhibition by β-catenin activation constitutes a mechanism to reduce inflammation.
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fig2: β-Catenin is an antagonist of the NF-κB pathway. In colon epithelial cells, Salmonella induces IL-8, TNFα, and Wnt expression via NF-κB activation. Moreover, the Salmonella typhimurium deubiquinating effector AvrA stabilizes IκBα and β-catenin. This step enhances β-catenin activity and at the same time inhibits NF-κB by stabilizing its inhibitor. The expression of Wnt in the first stage of infection stimulates Wnt/β-catenin pathway. The stabilized β-catenin then interacts with the NF-κB p50 subunit, decreasing its transcriptional activity. While NF-κB activity is inflammatory, its inhibition by β-catenin activation constitutes a mechanism to reduce inflammation.

Mentions: Infection of CEC with the avirulent Salmonella Phopc strain induced an increase of β-catenin phosphorylation at Ser552, a site associated with enhanced transcriptional activity, indicating that a protein effector is responsible for β-catenin stabilization [7]. In fact, the Salmonella effector protein AvrA has been shown to affect β-catenin stability because infection of CEC with the Salmonella strain SL1344 Phopc mutant that produces AvrA protein caused β-catenin stabilization, Wnt2/Wnt11 increased expression, and IL-6, IL-4, IFNγ, and TNFα decreased expression [11, 12]. A different in vitro and in vivo study has shown that Salmonella SL1344 strain activated NF-κB-dependent Wnt11/Wnt2 and IL-8 expression [10–12]. It is proposed that the deubiquitinase activity of AvrA inhibits βTRCP1-dependent ubiquitination of β-catenin and IκB, the cytoplasmic inhibitor of NF-κB. This AvrA inhibitory activity on ubiquitin ligases would make β-catenin more stable and the NF-κB transcriptional activity less effective (Figure 2). Furthermore, ectopic overexpression of Wnt11 and Wnt2 decreased NF-κB and AP-1 transcriptional activity [11, 12]. This evidence indicates that Wnt11 and Wnt2 trigger a negative feedback mechanism that controls NF-κB activity through β-catenin activation.


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)

β-Catenin is an antagonist of the NF-κB pathway. In colon epithelial cells, Salmonella induces IL-8, TNFα, and Wnt expression via NF-κB activation. Moreover, the Salmonella typhimurium deubiquinating effector AvrA stabilizes IκBα and β-catenin. This step enhances β-catenin activity and at the same time inhibits NF-κB by stabilizing its inhibitor. The expression of Wnt in the first stage of infection stimulates Wnt/β-catenin pathway. The stabilized β-catenin then interacts with the NF-κB p50 subunit, decreasing its transcriptional activity. While NF-κB activity is inflammatory, its inhibition by β-catenin activation constitutes a mechanism to reduce inflammation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: β-Catenin is an antagonist of the NF-κB pathway. In colon epithelial cells, Salmonella induces IL-8, TNFα, and Wnt expression via NF-κB activation. Moreover, the Salmonella typhimurium deubiquinating effector AvrA stabilizes IκBα and β-catenin. This step enhances β-catenin activity and at the same time inhibits NF-κB by stabilizing its inhibitor. The expression of Wnt in the first stage of infection stimulates Wnt/β-catenin pathway. The stabilized β-catenin then interacts with the NF-κB p50 subunit, decreasing its transcriptional activity. While NF-κB activity is inflammatory, its inhibition by β-catenin activation constitutes a mechanism to reduce inflammation.
Mentions: Infection of CEC with the avirulent Salmonella Phopc strain induced an increase of β-catenin phosphorylation at Ser552, a site associated with enhanced transcriptional activity, indicating that a protein effector is responsible for β-catenin stabilization [7]. In fact, the Salmonella effector protein AvrA has been shown to affect β-catenin stability because infection of CEC with the Salmonella strain SL1344 Phopc mutant that produces AvrA protein caused β-catenin stabilization, Wnt2/Wnt11 increased expression, and IL-6, IL-4, IFNγ, and TNFα decreased expression [11, 12]. A different in vitro and in vivo study has shown that Salmonella SL1344 strain activated NF-κB-dependent Wnt11/Wnt2 and IL-8 expression [10–12]. It is proposed that the deubiquitinase activity of AvrA inhibits βTRCP1-dependent ubiquitination of β-catenin and IκB, the cytoplasmic inhibitor of NF-κB. This AvrA inhibitory activity on ubiquitin ligases would make β-catenin more stable and the NF-κB transcriptional activity less effective (Figure 2). Furthermore, ectopic overexpression of Wnt11 and Wnt2 decreased NF-κB and AP-1 transcriptional activity [11, 12]. This evidence indicates that Wnt11 and Wnt2 trigger a negative feedback mechanism that controls NF-κB activity through β-catenin activation.

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