title: Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response.
abstract: Histamine, a major mediator in allergic diseases, differentially regulates the polarizing ability of dendritic cells after Toll-like receptor (TLR) stimulation, by not completely explained mechanisms. In this study we investigated the effects of histamine on innate immune reaction during the response of human monocyte-derived DCs (mDCs) to different TLR stimuli: LPS, specific for TLR4, and Pam3Cys, specific for heterodimer molecule TLR1/TLR2. We investigated actin remodeling induced by histamine together with mDCs phenotype, cytokine production, and the stimulatory and polarizing ability of Th0. By confocal microscopy and RT-PCR expression of Rac1/CdC42 Rho GTPases, responsible for actin remodeling, we show that histamine selectively modifies actin cytoskeleton organization induced by TLR4, but not TLR2 and this correlates with increased IL4 production and decreased IFNγ by primed T cells. We also demonstrate that histamine-induced cytoskeleton organization is at least in part mediated by down-regulation of small Rho GTPase CdC42 and the protein target PAK1, but not by down-regulation of Rac1. The presence and relative expression of histamine receptors HR1-4 and TLRs were determined as well. Independently of actin remodeling, histamine down-regulates IL12p70 and CXCL10 production in mDCs after TLR2 and TLR4 stimulation. We also observed a trend of IL10 up-regulation that, despite previous reports, did not reach statistical significance.
authors.affiliation: From the Departments of Neuroscience, Psychology, Drugs and Child Health.
authors.forename: Alessandra
authors.identifier: 0000-0003-4556-913X
authors.initials: A
authors.lastname: Aldinucci
authors.affiliation: From the Departments of Neuroscience, Psychology, Drugs and Child Health.
authors.forename: Elena
authors.initials: E
authors.lastname: Bonechi
authors.affiliation: Clinical and Experimental Medicine, and.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Manuelli
authors.affiliation: Clinical and Experimental Medicine, and.
authors.forename: Daniele
authors.identifier: 0000-0002-1903-5145
authors.initials: D
authors.lastname: Nosi
authors.affiliation: From the Departments of Neuroscience, Psychology, Drugs and Child Health.
authors.forename: Emanuela
authors.identifier: 0000-0001-6908-7720
authors.initials: E
authors.lastname: Masini
authors.affiliation: Health Sciences, University of Florence, Florence 50137, Italy.
authors.forename: Maria Beatrice
authors.identifier: 0000-0002-7729-9069
authors.initials: MB
authors.lastname: Passani
authors.affiliation: From the Departments of Neuroscience, Psychology, Drugs and Child Health, clara.ballerini@unifi.it.
authors.forename: Clara
authors.identifier: 0000-0002-7812-9029
authors.initials: C
authors.lastname: Ballerini
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D006632:Histamine
keywords: cytokine; cytoskeleton; dendritic cell; histamine; immunology; innate immunity