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2016 ; 17
(4
): 498
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Triptolide Modulates TREM-1 Signal Pathway to Inhibit the Inflammatory Response
in Rheumatoid Arthritis
#MMPMID27049384
Fan D
; He X
; Bian Y
; Guo Q
; Zheng K
; Zhao Y
; Lu C
; Liu B
; Xu X
; Zhang G
; Lu A
Int J Mol Sci
2016[Apr]; 17
(4
): 498
PMID27049384
show ga
Triptolide (TP), an active component isolated from Tripterygiumwilfordii Hook F,
has therapeutic potential against rheumatoid arthritis (RA). However, the
underlying molecular mechanism has not been fully elucidated. The aim of this
study is to investigate the mechanisms of TP acting on RA by combining
bioinformatics analysis with experiment validation. The human protein targets of
TP and the human genes of RA were found in the PubChem database and NCBI,
respectively. These two dataset were then imported into Ingenuity Pathway
Analysis (IPA) software online, and then the molecular network of TP on RA could
be set up and analyzed. After that, both in vitro and in vivo experiments were
done to further verify the prediction. The results indicated that the main
canonical signal pathways of TP protein targets networks were mainly centered on
cytokine and cellular immune signaling, and triggering receptors expressed on
myeloid cells (TREM)-1 signaling was searched to be the top one shared signaling
pathway and involved in the cytokine and cellular immune signaling. Further in
vitro experiments indicated that TP not only remarkably lowered the levels of
TREM-1 and DNAX-associated protein (DAP)12, but also significantly suppressed the
activation of janus activating kinase (JAK)2 and signal transducers and
activators of transcription (STAT)3. The expression of tumor necrosis factor
(TNF)-?, interleukin (IL)-1? and IL-6 in lipopolysaccharides (LPS)-stimulated
U937 cells also decreased after treatment with TP. Furthermore, TREM-1 knockdown
was able to interfere with the inhibition effects of TP on these cytokines
production. In vivo experiments showed that TP not only significantly inhibited
the TREM-1 mRNA and DAP12 mRNA expression, and activation of JAK2 and STAT3 in
ankle of rats with collagen-induced arthritis (CIA), but also remarkably
decreased production of TNF-?, IL-1? and IL-6 in serum and joint. These findings
demonstrated that TP could modulate the TREM1 signal pathway to inhibit the
inflammatory response in RA.
|Animals
[MESH]
|Anti-Inflammatory Agents/chemistry/pharmacology/*therapeutic use
[MESH]
|Antineoplastic Agents, Phytogenic/chemistry/pharmacology/*therapeutic use
[MESH]
free
free
free
