Cell-penetrating peptides and proteins: new inhibitors of allergic airways disease.
Cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) are peptides that have the ability to efficiently traverse cellular membranes, either alone or in association with molecular cargo. Several naturally occurring PTDs, including those from HIV TAT and Drosophila antennapedia, have this unique activity. Synthetic CPPs, such as polyarginine, also have the ability to enter cells and transport a variety of cargo. While the precise mechanism(s) of cellular entry for individual CPPs may vary, it is likely that uptake is mediated, at least in part, through endocytosis. Moreover, biological activity of cell-penetrating peptides and proteins has been clearly demonstrated in a number of in vitro and in vivo studies. Recently, cell-penetrating proteins targeting the Ras GTPase and the phospholipid kinase PI3K (phosphoinositide 3-kinase) have been shown to inhibit eosinophil trafficking and survival in vitro. These proteins, as well as CPPs targeting the STAT-6 transcription factor or the T-cell costimulatory molecule CTLA-4 (cytotoxic T lymphocyte-associated antigen-4), have also been tested in animal models of asthma. Data from several groups, including ours, indicate that these molecules inhibit airway eosinophilic inflammation, airway hyperresponsiveness (AHR), and mucus production in experimental allergic airways disease. Thus, CPPs targeting these and other signaling molecules may also effectively inhibit allergic airways disease in humans.
Kinyanjui
Margaret W
MW
Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada.
Fixman
Elizabeth D
ED
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D060908:CTLA-4 Antigen; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology*; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016328:NF-kappa B; D010455:Peptides; D050800:STAT6 Transcription Factor; D054322:tat Gene Products, Human Immunodeficiency Virus; C015462:polyarginine