Chaperonin 10 modulation of toll-like receptor-inducible cytokine and chemokine secretion
Methods of use of Chaperonin 10 (Cpn10) are provided for regulating Toll-like receptor signaling and/or Toll-like receptor inducible immunomodulator secretion. Cpn10 negatively regulates Toll-like receptor agonist-induced pro-inflammatory cytokine and chemokine secretion, examples being IL-6 and RANTES, respectively. Cpn10 positively regulates Toll-like receptor agonist-induced anti-inflammatory cytokine and chemokine secretion, an example being IL-10. These immunoregulatory activities of Cpn10 may be useful in the treatment of diseases, disorders and conditions resulting from excessive pro-inflammatory cytokine and chemokine secretion. This invention also relates to producing, designing and/or screening Cpn10 agonists and antagonists according to their ability to regulate Toll-like receptor signaling and/or Toll-like receptor inducible immunomodulator secretion.
1. A method of screening for a Chaperonin 10 (Cpn10) antagonist comprising the steps of:
forming a molecular complex comprising a Toll-like receptor, a Toll-like receptor agonist and Cpn10 in the presence and absence of a candidate Cpn10 antagonist; and
detecting whether formation of the molecular complex is prevented or disrupted by the presence of the candidate Cpn10 antagonist;
wherein a candidate Cpn10 antagonist detected to prevent or disrupt formation of the molecular complex is identified as a Cpn10 antagonist.
2. The method of claim 1 , wherein the Toll-like receptor is selected from the group consisting of TLR2 and TLR4.