| Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion -> Monitor Keywords |
|
|
 
Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretionRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain StructureChaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070275890, Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF INVENTION [0001] This invention relates to use of Chaperonin 10 for modulating Toll-like receptor signaling and/or Toll-like receptor inducible immunomodulator production and/or secretion. More particularly, this invention relates to modulation of Toll-like receptor inducible cytokine and chemokine secretion for treatment of diseases, disorders and conditions resulting from excessive immunomodulator secretion. This invention also relates to producing, designing and/or screening agonists and antagonists of Chaperonin 10. BACKGROUND OF THE INVENTION [0002] The Toll-like receptor family plays an important role in inflammation and immunity in insects, animals and plants. Toll-like receptors (TLRs) are expressed by cells of the mononuclear lineage including lymphocytes, macrophages and dendritic cells. [0003] TLR2 is activated by TLR2 agonists such as lipoteichoic acid and lipopeptides, which can be components of the outer wall of certain bacteria. [0004] TLR3 is activated by agonists such as double stranded RNA derived from viruses. TLR4 is activated by lipoproteins or lipopolysaccharide (LPS) or endotoxin, which is a component of the outer wall of gram-negative bacteria. [0005] TLR activation by pathogens, or by molecules derived therefrom, induces intracellular signaling that primarily results in activation of the transcription factor NF-.kappa.B (Beg, 2002, Trends Immunol. 2002 23 509-12.) and modulation of cytokine production. However, a series of other pathways can also be triggered, including p38 mitogen activated kinase, c-Jun-N-terminal kinase and extracellular signal related kinase pathways (Flohe, et al., 2003, J Immunol, 170 2340-2348; Triantafilou & Triantafilou, 2002, Trends Immunol, 23 301-304). The patterns of gene expression induced by ligation of the different TLRs are distinct but often overlap. For instance a large proportion of the genes upregulated by TLR3 agonists and double stranded RNA are also upregulated by TLR4 agonists and LPS (Doyle et al., 2002, Immunity, 17 251-263). TLR4 activation by LPS in macrophages results in TNF-.alpha., IL-12 IL-1.beta., RANTES and MIP1.beta. secretion (Flohe et al., supra; Jones et al., 2002, J Leukoc Biol, 69 1036-1044). [0006] Mammalian chaperonin 10 (also known as heat shock protein 10) was first described as a mitochondrial protein involved in protein folding, and is a homologue of the bacterial protein GroES. GroES and chaperonin 10 (Cpn10) oligomerise into seven member rings that bind as a lid onto a cup-like structure that comprises seven GroEL or Hsp60 molecules, which tether denatured proteins to the complex (Bukau & Horwich, 1998, Cell, 92 351-366; Hartl & Hayer-Hartl, 2002, Science, 295 1852-1858). Cpn10 is also frequently found at the cell surface (Belles et al., 1999, Infect Immun, 67 4191-4200; Feng et al., 2001, Blood, 97 3505-3512) and in the extracellular fluid (Michael et al., 2003, J Biol Chem, 278 7607-7616; Johnson et al., 2003, Cir Rev Immunol, 23 15-44). [0007] Cpn10 has also been shown to be a suppressive factor present early in pregnancy and has shown immunosuppressive activity in experimental autoimmune encephalomyelitis, delayed type hypersensitivity and allograft rejection models (Zhang et al., 2003, J Neurol Sci, 212 37-46; Morton et al., 2000, Immunol Cell Biol, 78 603-607). [0008] A recent study using Mycobacterium tuberculosis Cpn10 described in International Publication WO 02/40038, suggests that this molecule may have efficacy in treating disorders such as cancer, allergic reactions and/or conditions mediated by Th2-type immune responses. It is proposed that this may be achieved through induction of cytokines such as TNF-.alpha. and IL-6. [0009] However, the mechanism of action by which Cpn10, and in particular mammalian Cpn10, exerts its immunoregulatory effects has remained obscure. SUMMARY OF INVENTION [0010] Surprisingly, the inventors have demonstrated that Cpn10 regulates Toll-like receptor agonist-mediated stimulation of immunomodulator secretion. [0011] More particularly, Cpn10 down-regulates Toll-like receptor mediated induction of pro-inflammatory immunomodulators and positively regulates Toll-like receptor mediated induction of anti-inflammatory immunomodulator secretion. [0012] Thus, the invention in one broad form is directed to the modulation of Toll-like receptor signaling by chaperonin 10 (Cpn10). [0013] In a first aspect, the invention provides a method of regulating Toll-like receptor signaling in an animal, or in one or more cells, or tissues or organs derived therefrom, including the step of administering Cpn10, or a derivative of Cpn10, to the animal, cells, tissues or organs, to thereby regulate Toll-like receptor signaling. [0014] In a second aspect, the invention provides a method of regulating immunomodulator secretion in an animal, or in one or more cells, or tissues or organs derived therefrom, including the step of administering Cpn10, or a derivative of Cpn10, to the animal, cells, tissues or organs, to thereby regulate Toll-like receptor-inducible immunomodulator production and/or secretion. [0015] According to these aspects, the invention provides a method of regulating Toll-like receptor signaling and/or immunomodulator production and/or secretion to thereby modulate the immune response in an animal to prophylactically or therapeutically treat a disease, disorder or condition. [0016] Preferably, the disease, disorder or condition is selected from acute or chronic inflammatory diseases such as septic shock, inflammatory bowel disease, arthritis, psoriasis, heart disease, atherosclerosis, chronic pulmonary disease, cachexia, multiple sclerosis, GVHD, transplantation and cancer. [0017] According to the invention, Cpn10 preferably regulates a Toll-like receptor selected from the group consisting of TLR2, TLR3 and TLR4. [0018] More preferably, the Toll receptor is selected from the group consisting of TLR2 and TLR4. [0019] Even more preferably, the Toll-like receptor is TLR4. [0020] Suitably, Cpn10 regulates Toll-like receptor signalling and immunomodulator production and/or secretion that is stimulated, activated or induced by a Toll-like receptor agonist. [0021] The Toll-like receptor agonist may be a pathogen, a molecule derived from or produced by a pathogen, or may be a synthetic Toll-like receptor agonist. Continue reading about Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion... Full patent description for Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion or other areas of interest. ### Previous Patent Application: Phalloidin derivatives and methods for their synthesis Next Patent Application: Collagen mimics Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion patent info. IP-related news and info Results in 0.04458 seconds Other interesting Feshpatents.com categories: Tyco , Unilever , Warner-lambert , 3m 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
