43 results about "TLR5" patented technology

The invention provides an immunomodulatory flagellin peptide having substantially the same amino acid sequence GALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQ (SEQ ID NO:44), or a modification thereof, and having toll like receptor 5 (TLR5) binding. The immunomodulatory flagellin peptide also can have substantially the same amino acid sequence TQFSGVKVLAQDNTLTIQVGANDGETIDIDLKQINS QTLGLDTL (SEQ ID NO:45); EGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVNG (SEQ ID NO:46) or MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANF TANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQS (SEQ ID NO:47), or a modification thereof. Also provided is an immunomodulatory flagellin peptide having substantially the same amino acid sequence LQKIDAALAQVDTLRSDLGAVQNRFNSAITNL (SEQ ID NO:48), or a modification thereof, and having toll like receptor 5 (TLR5) binding. The immunomodulatory flagellin peptide also can have substantially the same amino acid sequence TLRSDLGAVQNRFNSAITNLGNTVNNLSS (SEQ ID NO:49) or EQAAKTTENPLQKIDAALAQVDTLRSDLGAVQNRFNSAITNLGNTVNNLSS (SEQ ID NO:50), or a modification thereof. Further provided is an immunomodulatory flagellin peptide having substantially the same amino acid sequence GALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAE ITQ (SEQ ID NO:44) and substantially the same amino acid sequence LQKIDAALAQVDTLRSDLGAVQNRFNSAITNL (SEQ ID NO:48), or a modification thereof, and having toll like receptor 5 (TLR5) binding. Methods of using immunomodulatory flagellin peptides additionally are provided.

The present invention provides compositions comprising one or more RNAi agents (e.g., siRNAs, shRNAs, or RNAi vectors) for the treatment of conditions and diseases mediated by (e.g., featuring IgE-mediated hypersensitivity), as well as systems for identifying RNAi agents effective for this purpose. The compositions are suitable for the treatment of allergic rhinitis and / or asthma. In certain embodiments of the invention the RNAi agent is targeted to a transcript that encodes a protein selected from the group consisisting of the FCεRIα chain, the FCεRIβ chain, c-Kit, Lyn, Syk, ICOS, OX40L, CD40, CD80, CD86, Re1A, Re1B, 4-1BB ligand, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, CD83, SLAM, common γ chain, and COX-2. In addition, the invention provides RNAi agent / delivery agent compositions and methods of use. In certain embodiments of the invention compositions comprising an RNAi agent are delivered by the respiratory route.

A composition comprising a pathogen associated molecular pattern (PAMP) protein that activates toll-like receptor 2 (TLR2) or toll-like receptor 5 (TLR5) signaling and at least two distinct antigens of Listeria monocytogenes. Amino acids, nucleotides, vectors, cell lines, and the methods for production and use of the compositions are provided.

It has long been known that eosinopenia is observed during acute bacterial infection yet the mechanism remains undefined. Herein, we investigated the consequence of exposure to microbial products, specfically bacterial lipopolysaccharide (LPS), on eosinophil production. We demonstrate that developing murine eosinophils transiently express mRNA for six Toll-like receptors (TLR5) with highest expression of TLR2 and TLR4 throughout eosinophil development and nearly undetectable levels on mature eosinophils. LPS stimulation of eosinophil progenitors ex vivo markedly inhibited IL-5- mediated cellular proliferation and expansion Further LPS adrninistratwn in vivo reduced numbers of eosinophil progenitors in the bone marrow and blood in mice. Notably, LPS effectively reduced eosinophilia even in hypereosinophilic mice induced by the IL-S transgene. Taken together, these findings identify a mechanistic explanation for eosinopenia following bacterial infections and a novel therapeutic strategy for depleting eosinophil progenitors and inhibiting peripheral eosinophilia in eosinophil associated diseases.

The invention discloses a mesenchymal stem cell for inhibiting tumor growth and a preparation method and an application, and relates to the technical field of the medicine. The provided mesenchymal stem cell for inhibiting the tumor growth is a TLR5 positive mesenchymal stem cell. The preparation method for the TLR5 positive mesenchymal stem cell is to separate TLR5 high-expression positive mesenchymal stem cells by using a flow-type or overexpress TLR5 on the mesenchymal stem cell. The invention further provides a cultural supernatant containing a serum-free medium and the TLR5 positive mesenchymal stem cell, and further provides applications of the TLR5 positive mesenchymal stem cell and the cultural supernatant for preparing an anti-tumor drug. The cultural supernatant in TLR5+MSC conditions has the remarkable inhibiting effects to the in-vitro proliferation, the migration and the clonality of a tumor cell. The TLR5-activated MSC is capable of remarkably improving the in-vitro killing activity of a NK cell. The TLR5-activated MSC is capable of inhibiting the tumor growth in Lewis lung cancer mice.

Disclosed herein are flagellin mutants having an enhanced activity of stimulating the toll-like receptor-5 (hereinafter referred to as ''TLR5''). More specifically, disclosed are flagellin mutants, prepared by point-mutating some of the amino acids of a TRL5 agonist flagellin so as to enhance the TRL-stimulating activity of the flagellin.

The present invention relates to methods and pharmaceutical compositions for the treatment of respiratory tract infections. More particularly, the present invention relates to a TLR5 agonist for use in a method for treating a respiratory tract infection.

The invention aims to disclose application of Cap-TFlg protein in preparing a PCV2 vaccine. TFlg is blended with a C terminal of PCV2Cap protein so as to be displayed on the surface of PCV2 VLPs, anda TLR5 passageway is activated to improve an immune effect of a PCV2 VLPs vaccine. By utilizing a bioinformatics means, through an independent design, ORF2 and flagellin (TFlg) genes of porcine circovirus 2 type are subjected to pronucleus codon optimization, and Cap and Cap-TFlg protein expression genes suitable for being high-efficiently expressed in escherichia coli are artificially synthesized. The Cap and Cap-TFlg VLPs provided by the invention and an appropriate adjuvant are mixed to immunize piglets, the immune response of the piglets can be remarkably improved through the Cap-TFlg VLPs, and better immunogenicity and protectiveness are realized.

The present invention provides compositions comprising one or more RNAi agents (e.g., siRNAs, shRNAs, or RNAi vectors) for the treatment of conditions and diseases mediated by (e.g., featuring IgE-mediated hypersensitivity), as well as systems for identifying RNAi agents effective for this purpose. The compositions are suitable for the treatment of allergic rhinitis and / or asthma. In certain embodiments of the invention the RNAi agent is targeted to a transcript that encodes a protein selected from the group consisting of the FCεRIα chain, the FCεRIβ chain, c-Kit, Lyn, Syk, ICOS, OX40L, CD40, CD80, CD86, Re1A, Re1B, 4-1BB ligand, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, CD83, SLAM, common γ chain, and COX-2. In addition, the invention provides RNAi agent / delivery agent compositions and methods of use. In certain embodiments of the invention compositions comprising an RNAi agent are delivered by the respiratory route.

Disclosed is a method for rapidly amplifying CD8+ T cells and functional cell subpopulations thereof in vitro. A TLR1 / 2 agonist, a TLR2 / 6 agonist and a TLR5 agonist or a combination of above agonists is added to a conventional culture system for in-vitro amplification of CD8+ T cells. Recombinant cytokines IL-2, IL-7 and IL-15 as well as magnetic beads coated with an anti-human CD3 antibody and an anti-human CD28 antibody can be further added to the culture system for continuous co-stimulation.

The invention belongs to the technical field of biology and in particular relates to an NF-kB dual-luciferase reporter cell for stably expressing swine TLR5 receptor genes and a construction method thereof. A cell line refers to HEK293-NF-kB cells in which the swine TLR5 receptor genes are transferred, and the HEK293-NF-kB cells refer to HEK293 cells in which NF-kB firefly luciferase and renilla luciferase are transferred. The invention provides the stable cell line used in detection for researching pTLR5 activated downstream NF-kB promoter report genes. The invention also provides a biological material for performing high-throughput screening on differentially expressed genes in stable cells in quiesced and activated states in an RNA-Seq technology, and lays a foundation and platform forfurther researching species specificity of TLR5.

Biomarkers useful for diagnosing and assessing the extent of coronary artery disease (CAD) are provided, along with kits for measuring their expression. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples. In a preferred embodiment, the biomarkers are organized into clustered groups. The expression level of the biomarkers within a group are highly correlated to each other in normal and disease states. Expression values of genes chosen from each of two, three, four or five of the clustered gene groups, A, B, C, D, E may be used. Alternatively, expression values of genes chosen from the groups are combined into a metagene. Preferred biomarkers include S100A12, S100A8, S100A9, BCL2A1, and F5 (group A); XK, P62, and FECH (group B); TUBB2 (group C); IFNG, PDGFB, VSIG4, and TNF (group D); CSF3R, TLR5, CD46, and NCF1 (group E); S100A12, S100A9, BCL2A1, TXN and CSTA (group I); OLIG1, OLIG2, ADORA3, CLC, and SLC29A1 (group II); and CBS and ARG1 (group IV).

The invention discloses a genetic molecular marking method for disease-resistant breeding of pigs, and application thereof. The genetic molecular marking method includes the following steps of firstly, screening and determining the variation points of the TLR5 genes of the pigs; secondly, amplifying sequences comprising the determined variation points; thirdly, performing SSCP (single stranded conformation polymorphism) analysis on the amplified products of the second step, and comprehensively detecting the genotypes of pig core groups; fourthly, analyzing the correlation between individual genotypes and important cytokines representing general disease resistance, and selecting samples having three of four PCR-SSCP bands of the amplified products as advantageous individuals in the disease-resistant breeding. The genetic molecular marking method for the disease-resistant breeding of the pigs has high accuracy and can be used for mass detection, thereby providing an effective molecular marker breeding measure for improving the immune response capability and general disease resistance of piglets; when a genetic molecular marker is applied to the disease-resistant breeding, the breeding progress can be accelerated.

Antisense oligonucleotide compounds, compositions and methods are provided for down regulating the expression of TLR5. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding TLR5. The compositions may also comprise antisense oligonucleotides targeted to nucleic acids encoding TLR5 in combination with other therapeutic and / or prophylactic compounds and / or compositions. Methods of using these compounds and compositions for down-regulating TLR5 expression and for prevention or treatment of diseases wherein modulation of TLR5 expression would be beneficial are provided.

This disclosure relates to methods for detecting a level of expression of one or more genes (or proteins) in a subject having or suspected of having cancer, and optionally treating the subject with anadenosine pathway antagonist, for example an adenosine A2A receptor (ADORA2A) antagonist, to treat the cancer. The genes (or proteins) include, without limitation, CD68, CD163, LBP, CCL2, CCL3, CCL7,CCL24, CCNE1, CD 14, CD300E, CD86, CD93, CLEC5A, CSF3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, DFNA5, ECEL1, EPB41L3, EHF, FUT7, GALM, GBP6, GPR157, HAS1, IL1A, IL-1[beta], IL23, IL24, IL5, IL6, IL8, INHBA, LAP3, LAYN, LOC100505585, MRPL11, NID1, OST4, PADI2, PID1, PLAUR, PPBP, PTGS2, RHCG, SERPINB2, SLC11A1, SLC7A7, SPON1, ST6GALNAC2, TBX21, THBS1, C1R, C1S, C4BPA, CCL11, CCL20, CXCL16, CXCL2,HAMP, HSD11B1, ITGAM, LIF, SAA1, TFRC, TLR5, TNFSF14, TREM2, APP, ATG10, BCL2, CCL15, CD24, CD46, CD59, CREB5, CX3CL1, CXCL14, CYFIP2, DEFB1, DPP4, ECSIT, EPCAM, IFIT1, IGF1R, ITGA6, ITGB3, MAP2K4, MAPK1, MASP1, PPARG, RORC, SPA17, STAT5B, TOLLIP, AKT3, BMI1, CD 164, CD34, CDH5, CREB1, DOCK9, ENG, HMGB1, ITGA1, JAM3, MAF, MAPK3, MAPK8, MCAM, MFGE8, NOTCH1, NRP1, PRKCE, SMAD2, TAL1, THY1, TNFSF12,TRAF6, TXNIP, VEGFA, S100A8, and / or WDR83OS.

The invention relates to a new ionizing radiation damage resistance function of polyethyleneimine (PEI) compounds, and its application. The PEI mainly has two structures comprising a linear structure (the molecular formula is (C2H5N)x) and a branched structure (the molecular formula is (C2H5N)x[-N(C2H6N)C2H4-]y), wherein each of x and y is an integer not lower than 1. The PEI can specifically activate a cell TLR5 acceptor mediated NF-kappaB signal channel. Results of experiment researches show that the PEI is weakly toxic to cells and animals, can substantially activate the cell TLR5 acceptor mediated NF-kappaB signal channel and display a dosage dependency, and can substantially reduce the mortality of ionizing radiation damaged mice and prolong the animal survival time. The new ionizing radiation damage resistance function of the PEI can be used for researching medicines for preventing and treating ionizing radiation damages and damages caused by radiotherapy.

In vitro method and kit for prognosis or prediction of the response of rheumatoid patients to treatment with TNF-α factor blocking agents, which comprises determining, in a blood sample from said patients, the expression level of at least one of the eight genes selected from the group: HLA-DRB3, EAT2, GNLY, CAMP, SLC2A3, IL2RB, MXD4 and TLR5 or combinations thereof and comparing said expression level to the expression values obtained from responsive and non-responsive patients who showed responsiveness to the treatment and those who showed non-responsiveness thereto.

The present disclosure relates to a composition for preventing or treating graft-versus-host disease (GVHD) containing a TLR5 agonist derived from flagellin as an active ingredient. The TLR5 agonist derived from flagellin according to the present disclosure exhibits an excellent therapeutic effect against GVHD, and thus may be developed as an active ingredient for a composition for the treatment, prevention or alleviation of GVHD.

The present invention relates, in part, to compositions and methods for enhancement of an immune response and for increased vaccine efficacy by stimulation of the TLR5 receptor, for example, with a recombinant TLR5 agonist (e.g., a flagellin-based agent or variant thereof).

The present invention provides improved pharmacologically optimized and deimmunized flagellin variants and methods of use that exhibit reduced immunogenicity and reduced inflammasome response while still retaining the ability to activate TLR5 signaling.

Disclosed herein are flagellin mutants having an enhanced activity of stimulating the toll-like receptor-5 (hereinafter referred to as “TLR5”). More specifically, disclosed are flagellin mutants, prepared by point-mutating some of the amino acids of a TRL5 agonist flagellin so as to enhance the TRL-stimulating activity of the flagellin.

The invention provides improved flagellin serving as an immunologic adjuvant, and a preparation method and an application of the improved flagellin. A salmonella typhimurium flagellin mutant of the improved flagellin has bioactivity of flagellin, and contains I411A mutation compared with the wild salmonella typhimurium flagellin. The salmonella typhimurium flagellin mutant of the improved flagellin can weaken TLR5 (toll-like receptor) mediated natural immune response, and has significant adjuvanticity.

The invention discloses an application of a TLR5 agonist in the preparation of pulmonary fibrosis treatment medicines, and the preferable TLR5 agonist is selected from stFla. The fibrosis which is a primary pathologic base of the disability causing and the death causing of many chronic diseases severely threatens the health and lives of people. The incidence rate and the fatality of the pulmonary fibrosis have continuously rising trends. The TLR5 agonist, preferably the TLR5 agonist selected from the stFla, disclosed in the invention can substantially reduce the mortality of bleomycin induced pulmonary fibrosis mice, activate the TLR5 signal path, substantially reduce the pulmonary inflammation reactions caused by the bleomycin, and mitigate the pulmonary tissue fibrosis degree caused by the bleomycin, comprising the pulmonary collagen deposition, the hydroxyproline content and the -SMA expression.

Compositions and method of increasing levels of apoA1 and / HDL in a subject in need thereof are provided. The compositions include one or more TLR5 agonists in a pharmaceutically acceptable carrier in an effective amount to increase the level of apoA1 and / or HDL in a subject. In a preferred embodiment, the composition is an oral formulation of the one or more TLR5 agonists. The disclosed methods include administering compositions containing the one or more TLR5 agonists to a subject in need thereof, in an effective amount to increase levels of apoA1 and / or HDL in the subject. In one preferred embodiment, the subject is at risk of developing atherosclerosis and / or coronary heart disease. In some embodiments, the subject is diagnosed as having atherosclerosis. The disclosed compositions can also be administered to subjects presenting with hyperlipidemia or hypercholesterolemia.