Browsing by Subject "TLR9"

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  • Ahtiainen, Laura; Mirantes, Cristina; Jahkola, Tiina; Escutenaire, Sophie; Diaconu, Iulia; Osterlund, Pamela; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli (2010)
  • Tenhu, Elina; Teräsjärvi, Johanna; Cruzeiro, Manuel Leite; Savonius, Okko; Rugemalira, Emilie; Roine, Irmeli; He, Qiushui; Pelkonen, Tuula (2020)
    Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) ofTLR4andTLR9are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPsTLR4rs4986790 (896A > G) andTLR9rs187084 (-1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes inTLR4was significantly higher in patients withHaemophilus influenzaemeningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2-5.4;p= 0.021), whereas the frequency of variant genotypes inTLR9was significantly lower in patients withH. influenzaemeningitis than controls (OR, 0.4; 95% CI, 0.2-0.9;p= 0.036). No such differences were found with other causative pathogens, such asStreptococcus pneumoniaeandNeisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variantTLR4genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52-109.80;p= 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07-131.49;p= 0.044) than those with the wild-typeTLR4genotype. Our study suggests an association betweenH. influenzaemeningitis and genetic variation betweenTLR4andTLR9in Angolan children.
  • Lanki, Mira; Seppänen, Hanna; Mustonen, Harri; Hagström, Jaana; Haglund, Caj (2019)
    Background The link between inflammation and carcinogenesis is indisputable. In trying to understand key factors at play, cancer research has developed an interest in the toll-like receptors (TLRs), which have shown signs of having prognostic value in various adenocarcinomas. We began investigating the expression of toll-like receptors 1, 3, 5, 7, and 9 to evaluate their prognostic value of patients with pancreatic ductal adenocarcinoma (PDAC). Methods We collected tumor biopsies from 154 stage I-III PDAC patients surgically treated at Helsinki University Hospital between 2002 and 2011, excluding patients undergoing neoadjuvant therapy. We used tissue microarray slides and immunohistochemistry to assess expression of TLRs 1, 3, 5, 7, and 9 in PDAC tissue. Immunopositivity scores and clinicopathological characteristics were subjected to Fisher's exact test or the linear-by-linear association test. For the survival analysis, we applied the Kaplan-Meier method and log-rank test, and the Cox regression proportional hazard model served for univariate and multivariate analyses. Results Strong TLR1 expression was observable in 60 (39%), strong TLR3 in 48 (31%), strong TLR5 in 58 (38%), strong TLR7 in 14 (9%), and strong TLR9 in 22 (14%) patients. The multivariate analysis showed strong TLR1 expression to associate with better survival than moderate, low, or negative expression (HR = 0.68; 95% CI 0.47-0.99; p = 0.044). Additionally, those few patients with tumors negative for TLR1, TLR3, TLR7, or TLR9 fared poorly (HR = 2.41; 95% CI 1.31-4.43; p = 0.005; n = 13). Conclusion Strong TLR1 expression suggested better prognosis in PDAC patients, whereas negative expression of TLR1, TLR3, TLR7, or TLR9 was a sign of poor prognosis.