title: Piperine impairs the migration and T cell-activating function of dendritic cells.
abstract: Piperine, a major alkaloid found in the fruits of black and long pepper plants, has anti-inflammatory properties; however, piperine's effect on dendritic cell (DC) migration and T cell-activating function has not been investigated. Bone marrow-derived mouse DCs that were matured in the presence of 100 μM piperine showed reduced in vitro migration in response to CCL21, as well as reduced in vivo migration to lymph nodes. In addition, piperine-treated DCs had reduced CCR7 expression and elevated CCR5 expression, as well as reduced expression of CD40 and class II major histocompatibility complex molecules and decreased nuclear accumulation of RelB. DC production of interleukin (IL)-6, tumor necrosis factor α, and monocyte chemoattractant protein-1 in response to lipopolysaccharide stimulation was also reduced following piperine treatment. Exposure to piperine during maturation therefore caused DCs to retain an immature phenotype, which was associated with a reduced capacity to promote T cell activation since co-culture of ovalbumin (OVA323-339)-specific T cells with OVA323-339-pulsed DCs that were previously matured in the presence of piperine showed reduced interferon-γ and IL-2 expression. OVA323-339-specific T cell proliferation was also reduced in vivo in the presence of piperine-treated DCs. Inhibition of DC migration and function by piperine may therefore be a useful strategy to down-regulate potentially harmful DC-driven T cell responses to self-antigens and transplantation antigens.
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Gemma
authors.initials: G
authors.lastname: Rodgers
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Doucette
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Soutar
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada; Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Liwski
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada; Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada; Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada. Electronic address: d.w.hoskin@dal.ca.
authors.forename: David W
authors.initials: DW
authors.lastname: Hoskin
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051841:Transcription Factor RelB / Q000276:immunology / Q000378:metabolism
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D019013:CD40 Antigens; D018925:Chemokines; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; C111390:OVA 323-339; D010446:Peptide Fragments; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C497594:Relb protein, mouse; D051841:Transcription Factor RelB; D010047:Ovalbumin; C008922:piperine
keywords: Cytokine; Dendritic cell; Migration; Piperine; T lymphocyte