3.3 TBⅡ mitigated DSS-induced colitis via inhibiting NLRP3
signaling
To comprehensively unveil the underlying mechanism involved in the
protective role of TBⅡ in the colon of DSS-induced colitis mice, RNA
sequencing of control, DSS and TBⅡ-treated colon tissue was performed.
First, KEGG analysis showed obvious enrichment of various inflammatory
signaling including NOD-like receptor signaling pathway, which played an
important role in intestinal immune response, and NLRP3 quickly became
an important regulator of intestinal homeostasis (Figure 3A and B). Heat
maps further showed that the enrichment of down-regulated genes treated
with TB-Ⅱ was significantly affected in multiple inflammatory pathway
signals with NOD-like receptor pathways
(Figure 3C). Given that the role of
NLRP3, an inflammasome with apoptosis-associated speck-like protein
(ASC) and the effector molecule pro-caspase-1 that is closely associated
with development of inflammatory bowel disease (IBD) (Bauer et al.,
2010), in NOD like receptor proteins has been extensively characterized
and studied (Dick, Sborgi, Rühl, Hiller & Broz, 2016), we subsequently
performed on the determination of NLRP3 expression. Similar to the
heatmap results, we confirmed that the protein expression levels of
NLRP3, ASC, CASP1 and IL-1β were obviously elevated in DSS-treated mice
compared with control mice, whereas TBⅡ treatment significantly
inhibited NLRP3 signaling-associated protein expression in a
dose-dependent manner (Figure 3D). Together, these results suggested
that the mitigation of TBⅡ in DSS-induced colitis may likely be related
to the inhibition of NLRP3 signaling.