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2016 ; 129
(9
): 1047-52
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Increased Expression of the NOD-like Receptor Family, Pyrin Domain Containing 3
Inflammasome in Dermatomyositis and Polymyositis is a Potential Contributor to
Their Pathogenesis
#MMPMID27098789
Yin X
; Han GC
; Jiang XW
; Shi Q
; Pu CQ
Chin Med J (Engl)
2016[May]; 129
(9
): 1047-52
PMID27098789
show ga
BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) are common inflammatory
myopathies whose immunopathogenic mechanisms remain poorly understood. The
NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a
type of cytoplasmic multiprotein inflammasome and is responsible for the
activation of inflammatory reactivations. Responding to a wide range of exogenous
and endogenous microbial or sterile stimuli, NLRP3 inflammasomes can cleave
pro-caspase-1 into active caspase-1, which processes the pro-inflammatory
cytokines pro-interleukin (IL)-1? and pro-IL-18 into active and secreted IL-1?
and IL-18. The NLRP3 inflammasome is implicated in infectious and sterile
inflammatory diseases. However, it remains unclear whether it is involved in the
pathogenesis of DM/PM, which we aim to address in our research. METHODS: In this
study, 22 DM/PM patients and 24 controls were recruited. The protein and RNA
expression of IL-1?, IL-18, NLRP3, and caspase-1 in serum and muscle samples were
tested and compared between the two groups. RESULTS: The serum IL-1? and IL-18
levels were significantly higher in DM/PM patients than those in the controls by
enzyme linked immunosorbent assay (ELISA, DM vs. control, 25.02 ± 8.29 ng/ml vs.
16.49 ± 3.30 ng/ml,P < 0.001; PM vs. control, 26.49 ± 7.79 ng/ml vs. 16.49 ± 3.30
ng/ml,P < 0.001). Moreover, the real-time quantitative reverse
transcription-polymerase chain reaction (qRT-PCR) showed that DM/PM patients
exhibited higher RNA expression of IL-1?, IL-18, and NLRP3 in the muscle (for
IL-1?, DM vs. control, P= 0.0012, PM vs. control, P= 0.0021; for IL-18, DM vs.
control, P= 0.0045, PM vs. control, P= 0.0031; for NLRP3, DM vs. control, P=
0.0017, PM vs. control, P= 0.0006). Moreover, the protein expression of NLRP3 and
caspase-1 in muscle samples of DM/PM patients were also significantly elevated
compared to that in the muscles of the controls. CONCLUSIONS: Our findings
demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of
DM/PM. High NLRP3 expression led to elevated levels of IL-1? and IL-18 and could
be one of the factors promoting disease progress.