[Objective] The paper aimed to clone the full length gene of Toll-like recep- tors （TLRs） in Japanese flounder （Paralichthys olivaceus）, and analyze their structural features and expression regularity. [Method] Th...[Objective] The paper aimed to clone the full length gene of Toll-like recep- tors （TLRs） in Japanese flounder （Paralichthys olivaceus）, and analyze their structural features and expression regularity. [Method] The full length cDNA sequence of Toll like receptor 1（TLR1） gene was identified from Japanese flounder head kidney by ho- mologous cloning and rapid amplification cDNA ends （RACE）. The bioinformatics and expression model of this gene was analyzed. [Result] The TLR1 cDNA was 2 947 bp, a 2 418 bp open reading frame （ORF）, encoding 805 amino acid （aa） residues, including signal peptide, six leucine-rich repeat（LRR） motifs, two transmembrane zones and one TolI/IL 1 receptor （TIR） domain. The molecular weight of the deduced protein was 91.15 KDa, and the isoelectric point was 6.49. The amino acid sequence of Japanese flounder TLR1 possessed 69%-35% identity with the TLRls of other verte- brates, further analysis showed that the TIR domain of Japanese flounder TLR1 shared 84%-62% identities with TIR domains in other vertebrates. Japanese flounder TLR1 protein firstly clustered with TLRls in Epinephelus coioides in the phylogenetic analysis. The transcription of Japanese flounder TLR1 was examined by real-time quantitative PCR, and its mRNA was mainly detected in liver, heart and spleen. [Conclusion] The results lay a foundation for further studying the functions of TLR1 and developing immune potentiator in Japanese flounder.展开更多
Toll-like receptors （TLRs） 7 and 8 are crucial in host defence against single-stranded RNA （ssRNA） viruses. Such viruses cause severe illnesses, which remain a serious medical burden in both industrialised and dev...Toll-like receptors （TLRs） 7 and 8 are crucial in host defence against single-stranded RNA （ssRNA） viruses. Such viruses cause severe illnesses, which remain a serious medical burden in both industrialised and developing countries. TLR7/8 downstream signaling leads tO a dramatic cellular stress associated with energy consumption. However, the molecular mechanisms of cell survival and adaptation to TLR7/8-induced stress, which give the cells an opportunity to initiate proper inflammatory reactions, are not clear at all. Here we report for the first time that ligand-induced activation of TLR7/8 leads to the accumulation of hypoxia-inducible factor 1 alpha （HIF-1α） protein in THP-1 human myeloid macrophages via redoxand reactive nitrogen species-dependent mechanisms. MAP kinases and phosphoinositol-3K are not involved in TLR7/8-mediated HIF-1α accumulation. Experiments with HIF-1α knockdown THP- 1 cells have clearly demonstrated that HIF-1α is important for the protection of these cells against TLR7/8-induced depletion of ATP. Thus, HIF-1α might support both cell survival and the production of pro-inflammatory cytokines upon TLR7/8 activation.展开更多
Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-a...Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-associated molecular patterns （PAMPs） by TLRs, either alone or in heterodimedzation with other TLR or non-TLR receptors, induces the production of signals that are responsible for the activation of genes important for an effective host defense, especially those of proinflammatory cytokines. Thus, TLRs are involved in the development of many pathological conditions including infectious diseases, tissue damage, and cancer especially. In this review, the contribution of TLRs to tumorgenesis is evaluated. We hope to provide new insight into the progression of cancer and more importantly into the potential for TLRs as targets of therapeutics.展开更多
Objective： To investigate whether remifentanil induced cardioprotecting effect is associated with expression of toll-like receptor 4 （TLR4）, nuclear factor rB （NF-r.B） and serum interleukin -6 （IL-6）. Methods：...Objective： To investigate whether remifentanil induced cardioprotecting effect is associated with expression of toll-like receptor 4 （TLR4）, nuclear factor rB （NF-r.B） and serum interleukin -6 （IL-6）. Methods： Fifty rabbits were randomly divided into 5 groups （n=10） according to the treatment： sham operation group （group A）, ischemla-reperfusion group （group B）, low-dose remifentanil group （group C）, mediate-dose remifentanil group （group D）, and high-dose remlfentanil group （group E） Myocardial TLR4 mRNA levels, NF-r.B protein expression and serum levels of IL-6 were observed in 120 min after reperfusion. Results： The myocardial expressions of TLR4 mRNA, NF-rd3 protein and IL-6 level in sera of groups B, C, D and E were elevated compared with group A. However, remifentanil significantly reduced the levels of TLR4 mRNA, NF- r.B protein expression and serum IL-6 in groups C, D and E compared with group B. There were remarkable differences between the groups （P〈O.O1）. Conclusion： Intravenous remifentanil has protective effect against rabbit myocardial ischemia/reperfusion injury. This effect may be associated with TLR4, NF-r.B expressions on myocytes and serum level of IL-6 in a dose-dependent manner展开更多
Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During ma...Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.展开更多
基金Supported by Natural Science Foundation of Tianjin City(10JCYBJC09100)Doctoral Fund of Tianjin Normal University(52XB1004)Open Research Fund for Municipal Key Laboratory of Tianjin Normal University~~
文摘[Objective] The paper aimed to clone the full length gene of Toll-like recep- tors （TLRs） in Japanese flounder （Paralichthys olivaceus）, and analyze their structural features and expression regularity. [Method] The full length cDNA sequence of Toll like receptor 1（TLR1） gene was identified from Japanese flounder head kidney by ho- mologous cloning and rapid amplification cDNA ends （RACE）. The bioinformatics and expression model of this gene was analyzed. [Result] The TLR1 cDNA was 2 947 bp, a 2 418 bp open reading frame （ORF）, encoding 805 amino acid （aa） residues, including signal peptide, six leucine-rich repeat（LRR） motifs, two transmembrane zones and one TolI/IL 1 receptor （TIR） domain. The molecular weight of the deduced protein was 91.15 KDa, and the isoelectric point was 6.49. The amino acid sequence of Japanese flounder TLR1 possessed 69%-35% identity with the TLRls of other verte- brates, further analysis showed that the TIR domain of Japanese flounder TLR1 shared 84%-62% identities with TIR domains in other vertebrates. Japanese flounder TLR1 protein firstly clustered with TLRls in Epinephelus coioides in the phylogenetic analysis. The transcription of Japanese flounder TLR1 was examined by real-time quantitative PCR, and its mRNA was mainly detected in liver, heart and spleen. [Conclusion] The results lay a foundation for further studying the functions of TLR1 and developing immune potentiator in Japanese flounder.
文摘Toll-like receptors （TLRs） 7 and 8 are crucial in host defence against single-stranded RNA （ssRNA） viruses. Such viruses cause severe illnesses, which remain a serious medical burden in both industrialised and developing countries. TLR7/8 downstream signaling leads tO a dramatic cellular stress associated with energy consumption. However, the molecular mechanisms of cell survival and adaptation to TLR7/8-induced stress, which give the cells an opportunity to initiate proper inflammatory reactions, are not clear at all. Here we report for the first time that ligand-induced activation of TLR7/8 leads to the accumulation of hypoxia-inducible factor 1 alpha （HIF-1α） protein in THP-1 human myeloid macrophages via redoxand reactive nitrogen species-dependent mechanisms. MAP kinases and phosphoinositol-3K are not involved in TLR7/8-mediated HIF-1α accumulation. Experiments with HIF-1α knockdown THP- 1 cells have clearly demonstrated that HIF-1α is important for the protection of these cells against TLR7/8-induced depletion of ATP. Thus, HIF-1α might support both cell survival and the production of pro-inflammatory cytokines upon TLR7/8 activation.
文摘Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-associated molecular patterns （PAMPs） by TLRs, either alone or in heterodimedzation with other TLR or non-TLR receptors, induces the production of signals that are responsible for the activation of genes important for an effective host defense, especially those of proinflammatory cytokines. Thus, TLRs are involved in the development of many pathological conditions including infectious diseases, tissue damage, and cancer especially. In this review, the contribution of TLRs to tumorgenesis is evaluated. We hope to provide new insight into the progression of cancer and more importantly into the potential for TLRs as targets of therapeutics.
基金Supported by Shaanxi Provincial Scientific and Technological Research Projects (2008K13-02)
文摘Objective： To investigate whether remifentanil induced cardioprotecting effect is associated with expression of toll-like receptor 4 （TLR4）, nuclear factor rB （NF-r.B） and serum interleukin -6 （IL-6）. Methods： Fifty rabbits were randomly divided into 5 groups （n=10） according to the treatment： sham operation group （group A）, ischemla-reperfusion group （group B）, low-dose remifentanil group （group C）, mediate-dose remifentanil group （group D）, and high-dose remlfentanil group （group E） Myocardial TLR4 mRNA levels, NF-r.B protein expression and serum levels of IL-6 were observed in 120 min after reperfusion. Results： The myocardial expressions of TLR4 mRNA, NF-rd3 protein and IL-6 level in sera of groups B, C, D and E were elevated compared with group A. However, remifentanil significantly reduced the levels of TLR4 mRNA, NF- r.B protein expression and serum IL-6 in groups C, D and E compared with group B. There were remarkable differences between the groups （P〈O.O1）. Conclusion： Intravenous remifentanil has protective effect against rabbit myocardial ischemia/reperfusion injury. This effect may be associated with TLR4, NF-r.B expressions on myocytes and serum level of IL-6 in a dose-dependent manner
文摘Toll-like receptors(TLRs) are a central component of innate immune system and play a major role as the initiator of the innate immune responses to defend against bacteria,viruses,parasite and other pathogens.During malaria infection,TLRs signaling pathways are initialed with the recognition of Plasmodium glycosylphosphatidylinositols(GPI) and hemozoin as pathogen-associated molecular patterns(PAMPs).And then,activation of TLRs signaling induces specific biological responses against malaria parasites invasion.However,TLRs are also involved in malaria pathogenesis and enhancement of immune tolerance and evasion for malaria infection.Moreover,malaria parasites regulate selectively TLRs expression on immune cells.Thus,these evidences indicated that TLRs have contrary roles on malaria infection.Understanding the complicated roles of TLRs on malaria infection will contribute us to design more effective anti-malaria drugs or vaccines.
