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Inflammasome Activation of Dermal Fibroblasts by an Endogenous Peptide Activate Tissue Resident Immune Cells (136.18)
Journal article   Peer reviewed

Inflammasome Activation of Dermal Fibroblasts by an Endogenous Peptide Activate Tissue Resident Immune Cells (136.18)

Carol Artlett, Sihem Sassi-Gaha and James Thacker
The Journal of immunology (1950), v 184(1_Supplement), pp 136-136.18
01 Apr 2010
DOI: https://doi.org/10.4049/jimmunol.184.Supp.136.18

Abstract

Abstract Activation of innate immunity is an important strategy for host defense as it is an early response to a pathogen derived danger signal. Recently, we discovered a lipopeptide 1-peptidyl-2,3-diacylglyceride that acts like a danger signaling molecule to induce an innate immune response. The peptide moiety alone (acALY-18) activates the inflammasome inducing the secretion of IL-1β, and subsequently IL6, IL8, MIP1α, and MCP1 in fibroblasts and keratinocytes. Subcutaneous administration of acALY-18 protected mice from a lethal dose of S. typhimurium (survival: 80% treated vs 0% untreated, P< 0.0001). We extended our initial observations with acALY-18 to further determine its effect in fibroblasts and subsequent effects on immune cells. Arrays confirmed the upregulation of IL1β, MIP1α, MCP1, and IL6; C8A, IL1α, IL1F8, IL1R2, IL1RN were also increased. THP1 cells responded to acALY-18 fibroblast conditioned media with the upregulation of CASP1 (2-fold), IL18 (2.6 fold), IL33 (7.5 fold), (IL1β 3600 fold), and IL6 (2.6 fold). The upregulation of IL1β and IL33 was greater than that observed in acALY-18 treated THP1 cells (2.5 fold and 1.6 fold respectively), suggesting that the fibroblast response to acALY-18 can mediate immune cell activation. Additional studies are further investigating the activation of the immune response by acALY-18. acALY-18 could directly translate to a novel therapeutic to enhance non-specific innate immune signaling against pathogens resistant to antibiotics.

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