Inhibitors of the interaction between HMGB polypeptides and toll-like receptor 2 as anti-inflammatory agents
View Patent ↗The invention features a method of treating an inflammatory condition in an individual, comprising administering an agent inhibits the interaction between a Toll-like receptor 2 (TLR2) and a high mobility group B (HMGB) polypeptide to the individual. The invention also features methods for identifying agents that inhibit the interaction between TLR2 and HMGB.
1. A method for inhibiting the release of a proinflammatory cytokine from a cell, comprising administering to said cell an effective amount of a soluble toll-like receptor 2 (sTLR2), and measuring the inhibition of HMGB 1-mediated release of a proinflammatory cytokine from the cell, wherein said sTLR2 comprises:
an amino acid sequence that has at least 95% sequence identity to amino acids 1-587 of SEQ ID NO: 46; that binds to a high mobility group box 1 (HMGB 1) polypeptide; and that inhibits HMGB 1-mediated release of a proinflammatory cytokine from a cell.
2. The method of claim 1 , wherein said HMGB1 polypeptide is mammalian.
3. The method of claim 1 , wherein said cell is a macrophage.
4. The method of claim 1 , wherein said proinflammatory cytokine is selected from the group consisting of tumor necrosis factor (TNF), interleukin-1 alpha (IL-1α), interleukin- 1 beta (IL-1β), macrophage migration inhibitory factor (MIF) and interleukin-6 (IL-6).
5. The method of claim 1 , wherein said cell is in an individual having or at risk for an inflammatory condition.
6. The method of claim 5 , wherein said inflammatory condition is selected from the group consisting Crohn's disease, sepsis, rheumatoid arthritis, systemic lupus erythematosus, endotoxic shock and allograft rejection.
7. A method for inhibiting the release of a proinflammatory cytokine from a cell, comprising administering to said cell an effective amount of a soluble toll-like receptor 2 (sTLR2), and measuring the inhibition of HMGB 1-mediated release of a proinflammatory cytokine from the cell, wherein said sTLR2 comprises an amino acid sequence that has at least 95% sequence identity to amino acids 1-587 of SEQ ID NO: 46, and wherein said sTLR2 binds to a high mobility group box 1 (HMGB 1) polypeptide and inhibits HMGB 1-mediated release of a proinflammatory cytokine from a cell.
8. A method for inhibiting the release of a proinflammatory cytokine from a cell, comprising administering to said cell an effective amount of a soluble toll-like receptor 2 (sTLR2), and measuring the inhibition of HMGB 1-mediated release of a proinflammatory cytokine from the cell, wherein said sTLR2 consists of an amino acid sequence that has at least 95% sequence identity to amino acids 1-587 of SEQ ID NO: 46, and wherein said sTLR2 binds to a high mobility group box 1 (HMGB 1) polypeptide and inhibits HMGB 1-mediated release of a proinflammatory cytokine from a cell.