2025-04-03 バーミンガム大学
<関連情報>
- https://www.birmingham.ac.uk/news/2025/pepitem-sequence-shows-effects-in-psoriasis-comparable-to-steroid-cream
- https://www.sciencedirect.com/science/article/pii/S1043661825000490?via%3Dihub
PEPITEM、そのトリペプチドファーマコフォアおよびそのペプチド模倣アナログは、腹膜炎および乾癬のモデルにおいて、非経口および局所投与により炎症反応を制御する PEPITEM, its tripeptide pharmacophores and their peptidomimetic analogues regulate the inflammatory response through parenteral and topical dosing in models of peritonitis and psoriasis
Anella Saviano, Bonita Apta, Samantha Tull, Laleh Pezhman, Areeba Fatima, Mustafa Sevim, Antonio Mete, Myriam Chimen, Anna Schettino, Noemi Marigliano, Helen M. McGettrick, Asif J. Iqbal, Francesco Maione, G. Ed Rainger
Pharmacological Research Available online: 22 January 2025
DOI:https://doi.org/10.1016/j.phrs.2025.107624
Graphical Abstract
Highlights
- Novel anti-inflammatory therapeutic agents.
- Tripeptides and peptidomimetics based on the PEPITEM sequence.
- Topical treatment of psoriasis with emollient cream.
- Reduced leukocyte trafficking and cytokine release.
- Resolution of local and systemic inflammatory processes.
Abstract
PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here, we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity in vivo. In a plaque psoriasis model, topical administration reduced disease severity, inflammation and immune cell infiltration, while regulating cytokine release in macrophages and fibroblasts, as well as keratinocyte proliferation. Th1 and Th17 cell abundance, along with their cytokines, was reduced in secondary lymphoid organs. This expanded functional repertoire of PEPITEM and its derivatives provides innovative tools for countering immune and stromal cell-induced pathology in IMIDs. Moreover, by identifying significantly smaller tripeptide pharmacophores of 14 amino acid PEPITEM, we may be able to deliver substantial financial advantages in synthesis and formulation. The order of magnitude increase in efficacy observed for some peptidomimetics may deliver agents with enhanced pharmacological characteristics compared to the parent PEPITEM sequence. Taken together with other reports on the efficacy of PEPITEM, this study paves the way for the development and translation of a novel class of anti-inflammatory agents which may have utility in a broad range of autoimmune and chronic inflammatory diseases.
