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2017 ; 8
(ä): 985
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Reactivation of Intestinal Inflammation Is Suppressed by Catestatin in a Murine
Model of Colitis via M1 Macrophages and Not the Gut Microbiota
#MMPMID28871257
Rabbi MF
; Eissa N
; Munyaka PM
; Kermarrec L
; Elgazzar O
; Khafipour E
; Bernstein CN
; Ghia JE
Front Immunol
2017[]; 8
(ä): 985
PMID28871257
show ga
While there is growing awareness of a relationship between chromogranin-A (CHGA)
and susceptibility to inflammatory conditions, the role of human catestatin
[(hCTS); CHGA(352-67)] in the natural history of established inflammatory bowel
disease is not known. Recently, using two different experimental models, we
demonstrated that hCTS-treated mice develop less severe acute colitis. We have
also shown the implication of the macrophages in this effect. The aims of this
study were to determine (1) whether hCTS treatment could attenuate the
reactivation of inflammation in adult mice with previously established chronic
colitis; (2) whether this effect is mediated through macrophages or the gut
microbiota. Quiescent colitis was induced in 7-8-week-old C57BL6 mice using four
cycles (2-4%) of dextran sulfate sodium. hCTS (1.5?mg/kg/day) treatment or
vehicle started 2?days before the last induction of colitis and continuing for
7?days. At sacrifice, macro- and microscopic scores were determined. Colonic
pro-inflammatory cytokines [interleukin (IL)-6, IL-1?, and TNF- ?],
anti-inflammatory cytokines (IL-10, TGF- ?), classically activated (M1) (iNOS,
Mcp1), and alternatively activated (M2) (Ym1, Arg1) macrophages markers were
studied using ELISA and/or RT-qPCR. In vitro, peritoneal macrophages isolated
from naïve mice and treated with hCTS (10(-5)?M, 12?h) were exposed to either
lipopolysaccharide (100?ng/ml, 12?h) to polarize M1 macrophages or to IL-4/IL-13
(20?ng/ml) to polarize M2 macrophages. M1/M2 macrophage markers along with
cytokine gene expression were determined using RT-qPCR. Feces and
mucosa-associated microbiota (MAM) samples were collected, and the V4 region of
16?s rRNA was sequenced. Micro- and macroscopic scores, colonic IL-6, IL-1?, TNF-
?, and M1 macrophages markers were significantly decreased in the hCTS-treated
group. Treatment did not have any effect on colonic IL-10, TGF-?, and M2 markers
nor modified the bacterial richness, diversity, or the major phyla in colitic
fecal and MAM samples. In vitro, pro-inflammatory cytokines levels, as well as
their gene expression, were significantly reduced in hCTS-treated M1 macrophages.
hCTS treatment did not affect M2 macrophage markers. These findings suggest that
hCTS treatment attenuates the severity of inflammatory relapse through the
modulation of the M1 macrophages and the release of pro-inflammatory cytokines.