|Title: ||Strategy to elucidate the receptor and pathway for the human antimicrobial peptide, cathelicidin LL-37|
|Authors: ||Vandamme, Dieter ×|
Schoofs, Liliane #
|Issue Date: ||Jun-2012 |
|Host Document: ||Proceedings of the 3rd International Symposium on Antimicrobial Peptides: Today knowledge and future applications|
|Conference: ||AMP2012 edition:3 location:Villeneuve d'Ascq (Lille) France date:13-15 June 2012|
|Abstract: ||Cathelicidins are, next to defensins, a multifunctional group of antimicrobial peptides. Since their discovery in 1991, it has become clear that this is an exceptional class of peptides. Not only do they execute an antibacterial , antifungal and antiviral function, they also show a chemotactic, immunostimulatory and immunomodulatory effect. Moreover, they are capable of inducing wound healing, angiogenesis and modulate apoptosis. Recent insights have even shown the role of this peptide in cancer.
It is our opinion that the cathelicidins are an understudied class of peptides. This is probably due to the surprisingly large array of different functions, on different types of microbes and eukaryotic cells, meaning that studying this class of antimicrobial peptides is very challenging. Hence we have applied an assay based on electrical impedance spectroscopy. This enables us to monitor cellular events such as cell proliferation, cytotoxicity, adhesion, viability, invasion, and migration in real time and in a label-free manner, using electronic cell sensor array technology. Real-time monitoring of cellular processes by this assay also offers distinct and important advantages over traditional end-point assays.
In recently performed experiments, this assay has provided us with more information about the effect of the human cathelicidin LL-37 on different eukaryotic cell lines. Using pharmacological blockers and our GPCR shRNA-plasmid library we intend to identify or confirm the receptors of LL-37. Additional information about the pathway is obtained by two-dimensional DIfferential Gel Electrophoresis (or 2D-DIGE) and Western blotting, as well as RNAi experiments and second messenger assays.
The results from these experiments are of great value, helping us to understand the complex but surprisingly logical actions of the cathelicidin peptide. This insight also enables us and colleague researchers to develop novel therapeutics, such as antibiotics, while predicting possible side effects. Moreover, knowledge about the mechanism of action of this peptide may also lead to novel therapeutics for diseases related to an aberrant production of the cathelicidin peptide, such as psoriasis, rosacea, chronic ulcers, cystic fibrosis, etc...
|Publication status: ||published|
|KU Leuven publication type: ||IMa|
|Appears in Collections:||Department of Pharmaceutical & Pharmacological Sciences - miscellaneous|
Animal Physiology and Neurobiology Section - miscellaneous