METHODS FOR INCREASING CATIONIC ANTIMICROBIAL PEPTIDES

摘要

Novel methods for enhancing or inducing the endogenous production of cationic antimicrobial peptides, preferably of defensins, more preferably of alpha defensins and beta defensins, most preferably beta defensins, in cells, preferably in epithelial cells, is provided. The method involves administering to cells either in vitro or in vivo, a CAP Stimulant and comprises the following steps: providing a CAP Stimulant, administering the CAP Stimulant to the cells. The CAP Stimulant comprises the inducer and optionally though preferably an aqueous carrier. The inducer is selected from the group consisting of: a bacterial cell wall extract inducer, a purified inducer, a peptidoglycan inducer and mixtures thereof. The purified inducer is preferably isolated and purified from the bacterial cell wall extract inducer. The bacterial cell wall extract inducer is preferably an extract of a commensal bacteria, such as for example, an oral bacteria, more preferably Fusobacterium, most preferably Fusobacterium nucleatum. The CAP Stimulant, when administered to cells, preferably epithelial cells, enhances the production of the cationic antimicrobial peptides, particularly defensins. Novel methods of detection of cationic antimicrobial peptide and the mRNA encoding such peptides, in cells whether the cells are in tissue, tissue samples, or in culture are provided. The methods of detection are useful for identifying individuals who are more prone to infection via the epithelia, due to low level production of cationic antimicrobial peptides. Thus, epithelial cells are removed from a patient, preferably mucosal cells, and the cells are cultured using conventional cell culture techniques. The CAP Stimulant is administered to the cultured cells, and the cationic antimicrobial peptide produced in response to the stimulant, is detected. Alternatively, the mRNA encoding such cationic antimicrobial peptides, is detected. The invention also relates to methods of making cationic antimicrobial peptides.