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2016 ; 291
(28
): 14803-14
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Histamine Regulates Actin Cytoskeleton in Human Toll-like Receptor 4-activated
Monocyte-derived Dendritic Cells Tuning CD4+ T Lymphocyte Response
#MMPMID27226579
Aldinucci A
; Bonechi E
; Manuelli C
; Nosi D
; Masini E
; Passani MB
; Ballerini C
J Biol Chem
2016[Jul]; 291
(28
): 14803-14
PMID27226579
show ga
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 IFN? 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.