Methods for attenuating release of inflammatory mediators and peptides useful therein

摘要

The present invention includes methods of inhibiting or suppressing cellular secretory processes. More specifically the present invention relates to inhibiting or reducing the release of inflammatory mediators from inflammatory cells by inhibiting the mechanism associated with the release of inflammatory mediators from granules in inflammatory cells. In this regard, the present invention discloses an intracellular signaling mechanism that illustrates several novel intracellular targets for pharmacological intervention in disorders involving secretion of inflammatory mediators from vesicles in inflammatory cells. Peptide fragments and variants thereof of MANS peptide as disclosed in the present invention are useful in such methods.

主权项

1. A method of inhibiting the MARCKS-related release of at least one inflammatory mediator from a granule in at least one inflammatory cell in a tissue and/or fluid of a subject comprising:
administration to said tissue and/or fluid a therapeutically effective amount of a pharmaceutical composition comprising a peptide having an amino acid sequence selected from the group consisting of: SEQ ID NOs: 106, 1, 11, 37, 45, 79, 91, 121, 143, 153, 219, 239, 248, 241, 251, 93, 108, 124, and 141, wherein the N-terminal amino acid of the peptide is chemically modified by acetylation; and wherein said peptide, optionally combined with a pharmaceutically acceptable carrier, and in a therapeutically effective inflammatory mediator release-reducing amount, reduces the amount of an inflammatory mediator released from at least one inflammatory cell as compared to release of said inflammatory mediator from at least one of the same type of inflammatory cell that would occur in the absence of said peptide.