FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387115570> ?p ?o ?g. }

• W4387115570 abstract "Toll-like receptor 4 (TLR4) is an innate immune receptor responsive to lipopolysaccharide (LPS). Single nucleotide polymorphisms (SNPs) in human TLR4 that encode an A896G transition at SNP rs4986790 (D299G) and a C1196T transition at SNP rs4986791 (T399I) render individuals hyporesponsive to LPS. In humans, these SNPs are also associated with increased susceptibility to inflammatory bowel diseases (IBDs). Using knock-in mice engineered to express the murine homologs of these human TLR4 mutations (TLR4-SNP mice), we have shown that TLR4-SNP mice develop significantly more severe colitis induced by dextran sodium sulfate (DSS) than wild-type (WT) mice, similar to IBD in humans expressing these SNPs. Previous studies have provided indirect evidence for tissue repair M2 macrophages (Mφ) in the resolution of colitis. Signaling through the IL-4/IL-13 receptor, IL-4Rα, and the transcription factor, peroxisome proliferator-activated receptor (PPARγ), have been shown to be required for induction of M2a Mφ, and our data provide direct evidence for the involvement of both in the repair of DSS-induced colonic damage. In response to DSS, colons of TLR4-SNP mice produced reduced levels of M2a Mφ marker mRNA and protein, including PPARγ, and therapeutic administration of the PPARγ agonist ligand, rosiglitazone, resolved colitis in TLR4-SNP mice, and increased expression of the M2a protein, Ym1. Together, these data indicate that the failure of TLR4-SNP mice to resolve DSS-induced colitis may be secondary to their failure to induce tissue repair M2a Mφ. IMPORTANCE Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, impacts millions of individuals worldwide and severely impairs the quality of life for patients. Dysregulation of innate immune signaling pathways reduces barrier function and exacerbates disease progression. Macrophage (Mφ) signaling pathways are potential targets for IBD therapies. While multiple treatments are available for IBD, (i) not all patients respond, (ii) responses may diminish over time, and (iii) treatments often have undesirable side effects. Genetic studies have shown that the inheritance of two co-segregating SNPs expressed in the innate immune receptor, TLR4, is associated with human IBD. Mice expressing homologous SNPs (TLR4-SNP mice) exhibited more severe colitis than WT mice in a DSS-induced colonic inflammation/repair model. We identified a critical role for M2a tissue repair Mφ in the resolution of colitis. Our findings provide insight into potential development of novel therapies targeting Mφ signaling pathways that aim to alleviate the debilitating symptoms experienced by individuals with IBD." @default.
• W4387115570 created "2023-09-29" @default.
• W4387115570 creator A5018165248 @default.
• W4387115570 creator A5041046556 @default.
• W4387115570 creator A5048079346 @default.
• W4387115570 creator A5064952582 @default.
• W4387115570 creator A5065617244 @default.
• W4387115570 creator A5069509653 @default.
• W4387115570 creator A5076905861 @default.
• W4387115570 creator A5089505596 @default.
• W4387115570 date "2023-09-28" @default.
• W4387115570 modified "2023-10-17" @default.
• W4387115570 title "M2a macrophages facilitate resolution of chemically-induced colitis in TLR4-SNP mice" @default.
• W4387115570 cites W1511083190 @default.
• W4387115570 cites W1520365933 @default.
• W4387115570 cites W1564743303 @default.
• W4387115570 cites W1577886890 @default.
• W4387115570 cites W1595293335 @default.
• W4387115570 cites W1596258860 @default.
• W4387115570 cites W1597676074 @default.
• W4387115570 cites W1606609113 @default.
• W4387115570 cites W1616145464 @default.
• W4387115570 cites W1824737122 @default.
• W4387115570 cites W1906569767 @default.
• W4387115570 cites W1937279395 @default.
• W4387115570 cites W1954354169 @default.
• W4387115570 cites W1964785649 @default.
• W4387115570 cites W1968143482 @default.
• W4387115570 cites W1968276290 @default.
• W4387115570 cites W1969354039 @default.
• W4387115570 cites W1976796596 @default.
• W4387115570 cites W1978926805 @default.
• W4387115570 cites W1984666000 @default.
• W4387115570 cites W1988104967 @default.
• W4387115570 cites W1988964423 @default.
• W4387115570 cites W1989233395 @default.
• W4387115570 cites W1989343973 @default.
• W4387115570 cites W1991081070 @default.
• W4387115570 cites W1991406147 @default.
• W4387115570 cites W1992591741 @default.
• W4387115570 cites W1992851871 @default.
• W4387115570 cites W1993930516 @default.
• W4387115570 cites W1997608954 @default.
• W4387115570 cites W1999816171 @default.
• W4387115570 cites W2003115027 @default.
• W4387115570 cites W2004465286 @default.
• W4387115570 cites W2004748614 @default.
• W4387115570 cites W2007489219 @default.
• W4387115570 cites W2008826892 @default.
• W4387115570 cites W2009170266 @default.
• W4387115570 cites W2012181682 @default.
• W4387115570 cites W2012650972 @default.
• W4387115570 cites W2013469022 @default.
• W4387115570 cites W2016675470 @default.
• W4387115570 cites W2017191185 @default.
• W4387115570 cites W2018075167 @default.
• W4387115570 cites W2019295440 @default.
• W4387115570 cites W2025648442 @default.
• W4387115570 cites W2026410196 @default.
• W4387115570 cites W2026981137 @default.
• W4387115570 cites W2028098820 @default.
• W4387115570 cites W2028627944 @default.
• W4387115570 cites W2033384515 @default.
• W4387115570 cites W2034178032 @default.
• W4387115570 cites W2038362257 @default.
• W4387115570 cites W2038486513 @default.
• W4387115570 cites W2038689279 @default.
• W4387115570 cites W2039973312 @default.
• W4387115570 cites W2040497359 @default.
• W4387115570 cites W2041006231 @default.
• W4387115570 cites W2043189165 @default.
• W4387115570 cites W2045225514 @default.
• W4387115570 cites W2046668733 @default.
• W4387115570 cites W2046905022 @default.
• W4387115570 cites W2047208232 @default.
• W4387115570 cites W2047947935 @default.
• W4387115570 cites W2048007675 @default.
• W4387115570 cites W2050650519 @default.
• W4387115570 cites W2051830262 @default.
• W4387115570 cites W2052757428 @default.
• W4387115570 cites W2052787972 @default.
• W4387115570 cites W2053484261 @default.
• W4387115570 cites W2054493318 @default.
• W4387115570 cites W2057842184 @default.
• W4387115570 cites W2058010499 @default.
• W4387115570 cites W2059842915 @default.
• W4387115570 cites W2061679773 @default.
• W4387115570 cites W2065442814 @default.
• W4387115570 cites W2067942093 @default.
• W4387115570 cites W2071187468 @default.
• W4387115570 cites W2073410163 @default.
• W4387115570 cites W2073578030 @default.
• W4387115570 cites W2075503219 @default.
• W4387115570 cites W2075762190 @default.
• W4387115570 cites W2077198680 @default.
• W4387115570 cites W2078621117 @default.
• W4387115570 cites W2082884465 @default.
• W4387115570 cites W2083089709 @default.
• W4387115570 cites W2088186564 @default.
• W4387115570 cites W2094464340 @default.

• next