34 results about "Interleukin-1 Converting Enzyme" patented technology

The present invention relates to a chimeric pro-caspase, which contains a pro-caspase domain and an oligomerizing domain. The invention also relates to an antibody that reacts specifically with a chimeric pro-caspase. In addition, the invention further relates to a polynucleotide encoding a chimeric pro-caspase, and to nucleotide sequences, which can hybridize specifically with a polynucleotide encoding a chimeric pro-caspase. The present invention also relates to a method of inducing apoptosis in a cell by providing a chimeric pro-caspase in the cell, wherein the chimeric pro-caspase includes a pro-caspase domain and an oligomerizing domain, whereby the chimeric pro-caspase forms an oligomer in the cell, thereby activating caspase activity of the chimeric pro-caspase and inducing apoptosis in the cell. The present invention further relates to a method of reducing the severity of a pathologic condition in a subject, by providing cells of the subject that are involved in the pathologic condition with a chimeric pro-caspase comprising a pro-caspase domain and an oligomerizing domain, whereby the chimeric pro-caspase forms an oligomer in the cells, thereby activating caspase activity of the chimeric pro-caspase, inducing apoptosis in the cells, and reducing the severity of the pathologic condition in the subject.

A method for treating a subject afflicted with an autoimmune disease with a pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier, comprising the steps of administering a therapeutic amount of the pharmaceutical composition to the subject, determining whether the subject is a glatiramer acetate responder or a glatiramer acetate hypo- / non-responder by measuring the value of a biomarker selected from the group consisting of IL-10 concentration, IL-17 concentration, IL-18 concentration, TNF-α concentration, BDNF concentration, caspase-1 concentration, IL-10 / IL-18 ratio and IL-10 / IL-17 ratio in the blood of the subject, and comparing the measured value to a reference value for the biomarker to identify the subject as a glatiramer acetate responder or a glatiramer acetate hypo- / non-responder, and continuing the administration if the subject is identified as a glatiramer acetate responder, or modifying treatment of the subject if the subject is identified as a glatiramer acetate hypo- / non-responder.

The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-γ-mediated diseases and decreasing IGIF and IFN-γ production using the compounds and compositions of this invention. This invention also relates to methods for preparing-N-acylamino compounds.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more biomarkers selected from the group consisting of Tumor necrosis factor receptor superfamily member 1OB, Cadherin-16, Caspase-9, Bcl2 antagonist of cell death, Caspase-1, Cadherin-1, Poly [ADP-ribose] polymerase 1, Cyclin-dependent kinase inhibitor 1, Cadherin-5, Myoglobin, Apolipoprotein A-II, Mucin-16, Carcinoembryonic antigen-related cell adhesion molecule 5, and Cellular tumor antigen p53 as diagnostic and prognostic biomarker assays in renal injuries.

The invention discloses application of evodiamine and rutaecarpine in preparation of a medicine for enhancing the activation of NLRP3 inflammasomes. The evodiamine and the rutaecarpine can generate active Caspase-1 by enhancing activiation of macrophage inflammasomes so as to release manure inflammatory mediators such as IL-1beta and promote pyroptosis of sensitized macrophages. The activity of the evodiamine and the rutaecarpine can be used for enhancing the inflammatory response intensity of a human body and treating related diseases of insufficient activation of inflammasome including pulmonary tuberculosis and oral tuberculosis caused by intracellular infection of mycobacterium tuberculosis, diseases caused by listeria monocytogenes, related diseases caused by other intracellular infection bacteria, related diseases caused by pathogenic fungal infection, furunculosis, dental-root periapical diseases, chronic gastritis, chronic enteritis, dysentery and diarrhea and the like.

The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1β converting enzyme (“ICE”) inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1-(“IL-1”), apoptosis-, interferon-γ inducing factor-(IGIF), or interferon-γ-(“IFN-γ”) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN-γ production and methods for treating interleukin-1, apoptosis-, and interferon-γ-mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.

To provide a microorganism and an ingredient thereof that contribute to prevention and treatment of immune diseases including allergy, autoimmune diseases and inflammatory bowel diseases (e.g., large-intestinal ulcer), a method of effectively selecting the microorganism, and a method of efficiently inducing immunoregulatory cells that play an important role on maintaining immunological homeostasis using the microorganism or the ingredient thereof. The present invention provides a Lactococcus and an ingredient thereof which induce production of IL-10 from mammalian dendritic or spleen cells, a method of obtaining the microorganism or the ingredient thereof by co-culturing a microorganism such as Lactococcus strains with mammalian dendritic or spleen cells to select a microbial cell having a high IL-10 production ability, a method of selecting the microorganism or the ingredient thereof by co-culturing an intestinal epithelial cell with a microorganism such as the lactic acid bacteria and selecting the cells on the basis of a caspase-1 activity and the ability of inducing the production of IL-18, and a food product or material and an animal feeding stuff or medical and pharmaceutical products which contain the lactic acid bacteria as an effective ingredient.

The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

The invention discloses a broad-spectrum anti-apoptosis rhabdovirus expression vector, and the broad-spectrum anti-apoptosis effect is achieved through the expression of the caspase-1 consensus sequence of target Spodoptera frugiperda and Trichoplusia ni insect cells by the vector. The rhabdovirus vector comprises a section of specific DNA sequence, the DNA sequence comprises the siRNA sequence ofthe consensus sequence of the target Sf-caspase-1 and Tn-caspase-1 transcribed by an RNA polymerase III promoter; the recombinant virus of the vector expresses double-strand small RNA in a host cell,the caspase-1 encoded by the silent host cell is interfered through the RNA, so that the apoptosis of the host cell is inhibited, and the expression level of a foreign protein is obviously improved.The broad-spectrum anti-apoptosis rhabdovirus expression vector can be used in the industrial production of protein preparations and vaccines.

To provide a microorganism and an ingredient thereof that contribute to prevention and treatment of immune diseases including allergy, autoimmune diseases and inflammatory bowel diseases (e.g., large-intestinal ulcer), a method of effectively selecting the microorganism, and a method of efficiently inducing immunoregulatory cells that play an important role on maintaining immunological homeostasis using the microorganism or the ingredient thereof. The present invention provides a Lactococcus and an ingredient thereof which induce production of IL-10 from mammalian dendritic or spleen cells, a method of obtaining the microorganism or the ingredient thereof by co-culturing a microorganism such as Lactococcus strains with mammalian dendritic or spleen cells to select a microbial cell having a high IL-10 production ability, a method of selecting the microorganism or the ingredient thereof by co-culturing an intestinal epithelial cell with a microorganism such as the lactic acid bacteria and selecting the cells on the basis of a caspase-1 activity and the ability of inducing the production of IL-18, and a food product or material and an animal feeding stuff or medical and pharmaceutical products which contain the lactic acid bacteria as an effective ingredient.

The present invention is based on two important experimental observations: The first observation is that increased extracellular concentrations of ionized calcium are found in erosive arthritis and stimulate monocytic IL-1β release via the CaSR and GPRC6A. Simultaneous stimulation of monocytes with calcium ions and selected TLR ligands results in a 20-fold increased IL1β response compared to lipopolysaccharide (LPS) alone. During the crosstalk between GPCR and TLR signaling, phospholipase C is activated, which triggers calcium dependent potassium channels, resulting in potassium efflux, caspase-1 activation and IL-1β release. The amplification of IL1β secretion at sites of locally increased calcium ion concentrations aggravates rheumatoid arthritis. The second important observation is that both CaSR and GPRC6A, are highly expressed in the synovial membrane of patients with rheumatoid arthritis, but expression of GPRC6A, but not of CaSR, is lower in patients with osteoarthritis (s. FIG. 1). The latter is generally not accompanied by inflammation. Thus, expression of GPRC6A appears to be upregulated in chronic inflammatory situations. Based on these experimental observations the invention provides a method and compositions for the identification of agents that have a potential effect against chronic inflammatory conditions, in particular erosive arthritis and atherosclerosis.

The invention discloses a caspase-1 inhibitor targeting liver. The caspase-1 inhibitor is formed by connection of human hepatitis B virus Pre-S1 peptide and caspase-1 inhibitor through a flexible connector, wherein the Pre-S1 peptide consists of amino acids from first to fiftieth of the Pre-S1 protein; and the caspase-1 inhibitor is formed by connection of trimolecular polymer of YVAD tetrapeptide and trimolecular polymer of VAD tripeptide. According to the inhibitor, the caspase-1 inhibitor is specifically targeted to a liver cell by utilizing the carrier Pre-S1 peptide which specifically targets liver, so that intrahepatic persistent chronic inflammation caused by endogenous danger signals released by injured liver cells can be blocked by terminating caspase-1 activation in the liver cell, sequential spinal cord injury of the liver cell can be blocked, body adverse response which is possibly caused by spread inhibition of caspase-1 can be reduced, and the liver cell can be specifically and effectively protected. The caspase-1 inhibitor can be used for preparing a medicament for treating intrahepatic chronic inflammation caused by endogenous danger signals released by injured liver cells.

The invention discloses application of an NALP3-ASC inflammation complex and an activator inhibitor thereof in terms of preparation of medicines for treating prion diseases. Experiments show that prion infects microgliacyte, NALP3-ASC inflammation complex enhanced caspase-1 and IL-1beta activation are formed. The inflammation complex NALP3 inhibitor can suppress NALP3 and ASC expression, and then suppresses activation and release of the caspase-1 and IL-1beta. The invention provides the application of the NALP3-ASC inflammation complex inhibitor for screening medicines for treating the prion diseases, by means of cell co-stimulation for a sample to be detected and the prion, total RNA (ribonucleic acid) of treated cells is extracted, NALP3 and ASC are detected by a qPCR (quantitative polymerase chain reaction) method, expression suppression conditions of the sample to mRNA (messenger ribonucleic acid) of the NALP3 and the ASC are judged according to PCR (polymerase chain reaction) amplification results, accordingly medicines for resisting Prion diseases are screened out, and effects of preventing, treating or controlling the prion diseases are realized.

The invention relates to a method for preparing antibody aiming at beet armyworm caspase-1. The method comprises the following steps: immunizing an animal through polypeptide as shown in SEQ ID NO: 1 of an amino acid sequence, collecting serum of the animal, and purifying antibody from the serum. The invention further discloses the antibody obtained through the method. The invention further discloses a method for detecting beet armyworm caspase-1 large-subunit through the antibody. Through the adoption of the method and the antibody, the beet armyworm caspase-1 large-subunit in a sample can be specifically detected, and moreover, excitation of caspase-1 protein during insect cell apoptosis is initially detected, that is, breakage of large and small-subunit is detected. The method has important significance for the research on the toxicological meaning of the insect caspase gene family and the development of a new pesticide taking caspase as a target.