We hypothesize that additional functional PU.1 site may increase TLR4 expression in individuals carrying minor C variant of rs7873784 and modulate the development of certain pathologies, such as rheumatoid arthritis and type-2 diabetes mellitus.
Genetic variants in the TLR4 gene or in the IRAK1 and TIRAP genes may have an important role in the development of insulin resistance and type 2 diabetes by disrupting the inflammatory response.
Inflammatory pathways induced by LPS, activation of toll-like receptor-4 (TLR-4), and other inflammatory signaling pathways are mediators of systemic inflammation, insulin resistance and type II diabetes mellitus.
Taken together, these findings may reveal a promotive role of TLR4 in regulating hyperglycaemia-induced catabolism and inflammation in T2DM-associated OA, and also implicate that TLR4 inhibition might be of therapeutic significance in treating T2DM-associated OA.
Toll-like receptor-4 (TLR-4) is the major pro-inflammatory pathway with its ligands and downstream products increased systemically in T2D and in at-risk individuals.
Although it remains unclear whether other signaling pathways (e.g., Wnt pathway) contribute to the T2D susceptibility of haplogroup N9a, our data indicate that in the case of mtDNA haplogroup N9a, T2D is affected, at least partially through ERK1/2 overstimulation and subsequent TLR4 activation.
The type 2 diabetes nephropathy model was built successfully, which along with increased urinary protein excretion rate and increased inflammatory infiltration, and the correlation was characterized by increased CD68<sup>+</sup>, F4/80<sup>+</sup> cells and increased TLR4, αSMA, SR expression.
The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear.
Toll-like receptor-4 (TLR4) is a major pro-inflammatory pathway; its ligands as well as downstream signals are increased systemically in patients with T2D and at-risk individuals.
These results indicate that WISP1 contributes to hepatic steatosis and skeletal muscle insulin resistance through a TLR4-activated inflammation/JNK signaling pathway and could be a useful therapeutic target for treatment of non-alcoholic fatty liver disease and type 2 diabetes.
KEGG and Reactome enrichment analysis indicated that mRNAs impact on cholinergic synapses, nuclear factor‑kB pathway, Toll like receptor 4 cascade and zinc transporter are correlated with cognitive dysfunction in type 2 diabetes.
Testing an association between TLR4 and CXCR1 gene polymorphisms with susceptibility to urinary tract infection in type 2 diabetes in north Indian population.
In this study, we have demonstrated a conclusive association with IL-1β-511 locus and IL-1β-511-TLR4-896 diplotype (CC-AA) and T2DM, which warrants further comprehensive analyses in larger cohorts.
TLR2 and TLR4 downward signaling causes the production of proinflammatory cytokines that can induce insulin resistance and cardiovascular damage in obesity and type 2 diabetes mellitus.
Among the proinflammatory mediators, the mRNA expression of MCP-1, IL1-β, NFκB, TLR2, and TLR4 were also significantly (<i>p</i> < 0.05) increased in T2DM.
These preliminary findings indicate that the g.13726T>C and g.15090G>A genetic polymorphisms of TLR4 gene are potentially related to the susceptibility to T2DM in the studied population, and might be used as molecular markers for evaluating the risk of T2DM.