Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28928749
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Immunol
2017 ; 8
(ä): 1088
Nephropedia Template TP
Dong G
; Song L
; Tian C
; Wang Y
; Miao F
; Zheng J
; Lu C
; Alsadun S
; Graves DT
Front Immunol
2017[]; 8
(ä): 1088
PMID28928749
show ga
Neutrophils play an essential role in the innate immune response to microbial
infection and are particularly important in clearing bacterial infection. We
investigated the role of the transcription factor FOXO1 in the response of
neutrophils to bacterial challenge with Porphyromonas gingivalis in vivo and in
vitro. In these experiments, the effect of lineage-specific FOXO1 deletion in
LyzM.Cre(+)FOXO1(L/L) mice was compared with matched littermate controls. FOXO1
deletion negatively affected several critical aspects of neutrophil function in
vivo including mobilization of neutrophils from the bone marrow (BM) to the
vasculature, recruitment of neutrophils to sites of bacterial inoculation, and
clearance of bacteria. In vitro FOXO1 regulated neutrophil chemotaxis and
bacterial killing. Moreover, bacteria-induced expression of CXCR2 and CD11b,
which are essential for several aspects of neutrophil function, was dependent on
FOXO1 in vivo and in vitro. Furthermore, FOXO1 directly interacted with the
promoter regions of CXCR2 and CD11b. Bacteria-induced nuclear localization of
FOXO1 was dependent upon toll-like receptor (TLR) 2 and/or TLR4 and was
significantly reduced by inhibitors of reactive oxygen species (ROS and nitric
oxide synthase) and deacetylases (Sirt1 and histone deacetylases). These studies
show for the first time that FOXO1 activation by bacterial challenge is needed to
mobilize neutrophils to transit from the BM to peripheral tissues in response to
infection as well as for bacterial clearance in vivo. Moreover, FOXO1 regulates
neutrophil function that facilitates chemotaxis, phagocytosis, and bacterial
killing.
free
free
free
