ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Roles of TIR domain-containing adaptor protein in tumor: Inflammation and immune regulation via toll-like receptor signaling.The Journal of international medical research · 2026Review
- Coexisting PTEN and SDHB Mutations in a Pediatric Patient with PTEN Hamartoma Tumor Syndrome: a case report.Frontiers in pediatrics · 2026Article
- Imperative role of adaptor proteins in macrophage toll-like receptor signaling pathways.Future science OA · 2024Review
- TIRAP, TRAM, and Toll-Like Receptors: The Untold Story.Mediators of inflammation · 2023Review
- Naïve CD4International journal of molecular sciences · 2022Article
- Morin Inhibits Dox-Induced Vascular Inflammation By Regulating PTEN/AKT/NF-κB Pathway.Inflammation · 2022Article
- The Roles of Inflammasomes in Host Defense againstPathogens (Basel, Switzerland) · 2021Review
- Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor.Frontiers in physiology · 2021Review
- Alisol B 23-Acetate Ameliorates Azoxymethane/Dextran Sodium Sulfate-Induced Male Murine Colitis-Associated Colorectal CancerFrontiers in cellular and infection microbiology · 2021Article
- Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder-Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection.International journal of molecular sciences · 2020Article
- Pten gene deletion in intestinal epithelial cells enhances susceptibility to Salmonella Typhimurium infection in mice.Journal of microbiology (Seoul, Korea) · 2019Article
- Differential expression of tumor-associated genes and altered gut microbiome with decreased Akkermansia muciniphila confer a tumor-preventive microenvironment in intestinal epithelial Pten-deficient mice.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- Colonic Inhibition of Phosphatase and Tensin Homolog Increases Colitogenic Bacteria, Causing Development of Colitis in Il10-/- Mice.Inflammatory bowel diseases · 2018Article
- Nuclear PTEN enhances the maturation of a microRNA regulon to limit MyD88-dependent susceptibility to sepsis.Science signaling · 2018Article
- Src family kinase tyrosine phosphorylates Toll-like receptor 4 to dissociate MyD88 and Mal/Tirap, suppressing LPS-induced inflammatory responses.Biochemical pharmacology · 2018Article
- AThe EMBO journal · 2017Article
- Multi-receptor detection of individual bacterial products by the innate immune system.Nature reviews. Immunology · 2017Review
- MyD88 Adapter-like (Mal)/TIRAP Is Required for Cytokine Production by Splenic Ly6CloTLR2hi but Not by Ly6ChiTLR2hi Monocytes during Trypanosoma cruzi Infection.The Journal of biological chemistry · 2016Article
- Corticotropin Releasing Hormone and Urocortin 3 Stimulate Vascular Endothelial Growth Factor Expression through the cAMP/CREB Pathway.The Journal of biological chemistry · 2015Article
- Common and specific downstream signaling targets controlled by Tlr2 and Tlr5 innate immune signaling in zebrafish.BMC genomics · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Defective IL-10 allele is a risk factor for intestinal inflammation. Indeed, IL-10(-/-) mice are predisposed to spontaneous colitis in the presence of intestinal microbiota, indicating that microbial factors contribute to developing intestinal inflammation. By recognizing flagellin, TLR5 plays a quintessential role in microbial recognition in intestinal epithelial cells. Here, we treated flagellin (1.0 μg/mouse/d) in mouse colon and found that it elicited colonic inflammation in IL-10(-/-) mice, characterized with tissue hypertrophy, inflamed epithelium, and enhanced cytokine production in the colon (MPO, KC, IL-6; ≥2-fold; P < 0.05). These inflammatory effects were dramatically inhibited in TLR5(-/-);IL-10(-/-) mice. Intestinal epithelium specific PTEN deletion significantly attenuated flagellin-promoted colonic inflammation in IL-10(-/-) mice. As a molecular mechanism that PTEN deletion inhibited TLR5-elicited responses, we hypothesized that PTEN regulated TLR5-induced responses by controlling the involvement of Mal in TLR5 engagement. Mal interacted with TLR5 on flagellin, and Mal deficiency inhibited flagellin-induced responses in intestinal epithelial cells. Similarly, Mal(-/-);IL-10(-/-) mice showed reduced flagellin-promoted responses. Furthermore, PTEN deletion disrupted Mal-TLR5 interaction, resulting in diminished TLR5-induced responses. PTEN deletion impeded Mal localization at the plasma membrane and suppressed Mal-TLR5 interaction. These results suggest that, by controlling Mal recruitment, PTEN regulates TLR5-induced inflammatory responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.