antibody constant region peptides can display immunomodulatory activity through activation of the dectin-1 signalling pathway抗体恒定区多肽可以显示免疫调节活动通过dectin-1信号通路的激活.pdfVIP

Antibody Constant Region Peptides Can Display Immunomodulatory Activity through Activation of the Dectin-1 Signalling Pathway 1. 1. 1 1 2 2 Elena Gabrielli , Eva Pericolini , Elio Cenci , Claudia Monari , Walter Magliani , Tecla Ciociola , 2 3 1 2 1 Stefania Conti , Rita Gatti , Francesco Bistoni , Luciano Polonelli , Anna Vecchiarelli * 1 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy, 2 Microbiology Section, Department of Pathology and Laboratory Medicine, University of Parma, Parma, Italy, 3 Histology Section, Department of Experimental Medicine, University of Parma, Parma, Italy Abstract We previously reported that a synthetic peptide with sequence identical to a CDR of a mouse monoclonal antibody specific for difucosyl human blood group A exerted an immunomodulatory activity on murine macrophages. It was therapeutic against systemic candidiasis without possessing direct candidacidal properties. Here we demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic cleavage of the constant region (Fc) of human IgG1, is able to induce IL-6 secretion and pIkB-a activation. More importantly, it causes an up-regulation of Dectin-1 expression. This leads to an increased activation of b-glucan-induced pSyk, CARD9 and pIkB-a, and an increase in the production of pro-inflammatory cytokines such as IL-6, IL-12, IL-1b and TNF-a. The increased activation of this pathway coincides with an augmented phagocytosis of non opsonized Candida albicans cells