Journal of Immunology Research

Research Article

Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD

Table 4

(a) The cytokines and chemokines upregulated in NASH/NAFLD were differentially expressed in caspase-11 and caspase-1 knockout. Among 28 cytokines and chemokines upregulated in NASH/NAFLD, caspase-11 deficiency upregulated 18 out of 28 (64.3%) and downregulated 8 out of 28 (28.6%) NASH/NAFLD-upregulated cytokines and chemokines. Caspase-1 deficiency upregulated one cytokine CXCL14 out of 39 (2.6%) and downregulated one cytokine LTB out of 39 (2.6%) NASH/NAFLD-upregulated cytokines and chemokines. (b) The upregulated canonical inflammasome regulators in NASH/NAFLD were differentially expressed in caspase-11 knockout. Caspase-11 deficiency upregulated 5 out of 28 (17.9%) and downregulated five out of 28 (17.9%) canonical inflammasome regulators induced by NASH/NAFLD. Caspase-1 deficiency did not modulate the expression of canonical inflammasome regulators induced by NASH/NAFLD. (c) The upregulated trained immunity enzyme genes in NASH/NAFLD were differentially expressed in caspase-11 knockout and caspase-1 knockout mouse models. Caspase-11 deficiency upregulated 6 out of 68 (8.8%) and downregulated 31 out of 68 (45.6%) trained immunity enzymes upregulated in NASH/NAFLD. Caspase-1 deficiency upregulated 4 out of 68 (5.9%) and downregulated 6 out of 68 (8.8%) trained immunity enzymes upregulated in NASH/NAFLD. (d) The upregulated lipid peroxidation enzyme genes in NASH/NAFLD were differentially expressed in caspase-11 knockout and caspase-1 knockout mouse models. Caspase-11 deficiency upregulated 13 out of 46 (28.3%) and downregulated 6 out of 46 (13%) lipid peroxidation enzymes upregulated in NASH/NAFLD. Caspase-1 deficiency upregulated 3 out of 46 (6.5%) and downregulated 6 out of 46 (13%) lipid peroxidation enzymes upregulated in NASH/NAFLD.
(a)
GEO IDGSE115094GSE32515
ComparisonCaspase-11-KO vs. WTCaspase-1-KO vs. WT
Gene symbol
 CXCL101.98
 CCL205.07
 EDN13.45
 CXCL162.50
 CKLF2.83
 CCL54.81
 TIMP110.52
 CCL24.75
 Ccl75.99
 TNF2.72
 TSLP7.42
 CCL82.70
 IL274.15
 PF44.82
 CCL1713.15
 CCL33.58
 CCL47.09
 CXCL54.50
 CXCL143.219
 DKK 3-5.54
 CX3CL1-4.49
 CXCL12-3.50
 CSF1-3.04
 TNFSF10-2.23
 NAMPT-2.08
 WNT5A-1.79
 SPP1-5.87
 LTB-1.551
% up18/39 (46.2%)1/39 (2.6%)
% down8/39 (20.5)1/39 (2.6%)
(b)
Canonical inflammasome pathway regulators upregulated in NASH
GEO IDGSE115094GSE32515
ComparisonCaspase-11-KO vs. WTCaspase-1-KO vs. WT
Gene symbol
 TXN21.749
 PYCARD2.469
 Naip51.602
 Naip21.895
 CYBA3.599
 PRKCD-1.643
 ANTXR2-3.523
 CTSB-2.328
 NAMPT-2.083
 RIPK1-1.754
% up5/28 (17.9%)0/28 (0%)
% down5/28 (17.9%)0/28 (0%)
(c)
Trained immunityGEO IDGSE115094GSE32515
PathwaysComparisonCaspase-11-KO vs. WTCaspase-1-KO vs. WT
GlycolysisLDHB2.520
PFKFB31.844
ALDOA1.883
FBP14.254
ALDOA1.883
ADH71.624
PFKFB11.511
PFKFB21.606
HK1-2.535
HK2-4.554
HKDC1-1.550
PDHA1-3.277
PFKFB4-1.570
PFKP-1.544
PGAM1-2.484
ENO1-1.689
DLAT-1.770
GALM-1.700
PANK1-1.892
PFKL-4.133
PGM2-1.663
PKLR-3.863-2.354
ALDH1B1-2.881
ALDH2-2.171
ALDH3A2-1.840
DLAT-1.770
ACSS2-1.836
ADH4-2.019
GCK-3.334
SLC2A2-1.789
ACSS1-3.206
ALDH1B1-2.881
ALDH2-2.171
ALDH3A2-1.840
MevalonatePMVK1.699
IDI1-3.248
HMGCS1-1.818
HMGCR-1.894
ACAT1-1.917
IDI1-3.248
Acetyl-CoA generationGOT1-1.6841.701
BDH1-1.964
ACO1-1.601
ACLY-2.203-2.33
% up6/68 (8.8%)4/68 (5.9%)
% down31/68 (45.6%)6/68 (8.8%)
(d)
Lipid peroxidationGEO IDGSE115094GSE32515
EnzymesComparisonCaspase-11-KO vs. WTCaspase-1-KO vs. WT
COXsCOX145.806
COX181.862
COX5B6.309
COX6A15.582
COX6B212.677
COX7A111.346
COX7C11.363
COX194.005
COX15-3.650
CYPsCYP2R14.459
CYP2B107.4684.070
CYP2C3915.441
CYP4A311.831
CYP2U1-2.833
CYP1B1-2.058
CYP20A1-2.466
CYP2B9-3.075
CYP2C37-6.050
CYP2C38-3.200
CYP2C54-2.609
CYP2C55-6.187
CYP4F18-1.575
GPXGPX46.696
GPX73.769
GPX83.769
GPX3-1.549
AA metabolismPLA2G6-2.293
% up13/46 (28.3%)3/46 (6.5%)
% down6/46 (13%)6/46 (13%)