Role of Toll-like receptors in gastrointestinal malignancies

Fukata, Masayuki; Abreu, María T.

doi:10.1038/sj.onc.1210908

Cited by 170 publications

(151 citation statements)

References 112 publications

(138 reference statements)

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…It was shown that a deficiency in the TLR adaptor, MyD88, significantly reduced tumor number and size in the Apcmin/ þ mouse model of intestinal tumorigenesis (Rakoff-Nahoum and Medzhitov, 2007). Furthermore, the absence of bacteria in several mouse models of inflammation-associated cancer has resulted in abrogation of dysplasia or cancer (Fukata and Abreu, 2008). Thus, the presence and recognition of a b c d Figure 1 Colitis-associated cancer.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory bowel disease and intestinal cancer: a paradigm of the Yin–Yang interplay between inflammation and cancer

Danese¹,

2010

View full text Add to dashboard Cite

Colon cancer represents a paradigm for the connection between inflammation and cancer in terms of epidemiology and mechanistic studies in preclinical models. Key components of cancer promoting inflammation include master transcription factors (for example, nuclear factor jB, STAT3), proinflammatory cytokines (for example, tumor necrosis factor, interleukin-6 (IL-6)), cyclooxygenase-2 and selected chemokines (for example, CCL2). Of no less importance are mediators that keep inflammation in check, including IL-10, transforming growth factorb, toll-like receptor and the IL-1 receptor inhibitor TIR8/ SIGIRR, and the chemokine decoy and scavenger receptor D6. Dissection of molecular pathways involved in colitis-associated cancer may offer opportunities for innovative therapeutic strategies.

show abstract

Section: Toll-like Receptorsmentioning

confidence: 99%

“…Polymorphisms in TLR4 have been associated with UC and CD (Fukata and Abreu, 2008). TLR4 is upregulated in intestinal epithelial cells in active CD and UC (Cario and Podolsky, 2000), and its signaling induces COX-2, prostaglandin E2 and reactive oxygen species (Fukata and Abreu, 2008).…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Inflammatory bowel disease and intestinal cancer: a paradigm of the Yin–Yang interplay between inflammation and cancer

Danese¹,

2010

View full text Add to dashboard Cite

show abstract

“…The inflammatory responses elicited were demonstrated to be able to enhance cancer progression. 152 Bacteria represent a continuous stimulus for maintaining activated immunity in the gut mucosa and actively participate in the metabolism of bile and food components. Since germ-free mice lack this stimulus, they serve as a useful tool to study the role of bacteria in intestinal carcinogenesis.…”

Section: Cancermentioning

confidence: 99%

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

et al. 2011

View full text Add to dashboard Cite

“…For both NF-κB and NFAT transcription pathways, bacteria, including some forms of commensal bacteria (11), are key driving factors. These observations suggest that the microbiome could be a source of direct stimuli for constitutive COX-2 expression, particularly in the gut and other barrier tissues.…”

mentioning

confidence: 99%

Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-κB and NFAT transcriptional pathways

Kirkby

Chan

Zaiss

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

146

115

View full text Add to dashboard Cite

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system. cyclooxygenase | nonsteroidal antiinflammatory drugs | prostacyclin | cardiovascular | Vioxx C yclooxygenase (COX) converts arachidonic acid to prostanoids, which include prostaglandins (PGs), prostacyclin, and thromboxane. Prostanoids are important mediators that regulate diverse functions in the cardiovascular, gastrointestinal, urogenital, and nervous systems, as well as playing critical roles in immunity, inflammation and resolution of inflammation. There are two COX

show abstract

Role of Toll-like receptors in gastrointestinal malignancies

Cited by 170 publications

References 112 publications

Inflammatory bowel disease and intestinal cancer: a paradigm of the Yin–Yang interplay between inflammation and cancer

Inflammatory bowel disease and intestinal cancer: a paradigm of the Yin–Yang interplay between inflammation and cancer

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-κB and NFAT transcriptional pathways

Contact Info

Product

Resources

About