676 11 FEBRUARY 2022¥VOL 375 ISSUE 6581 science.orgSCIENCE
A
B C
K
WT
Pla2g7
KO
0
2
4
6
8
10
ASC speck
% of containing ASC cells
**
Actin
LysoPC
OxPAPC
WT WT KO WT KO WT KO
20kDa
ProCasp1
Casp1
LPS LPS+Ceramide
WT
Pla2
g7KO
0
20
40
60
80
WT
Pla
2g7KO
0
1
2
3
4 *
WT
Pla2
g7KO
0
20
40
60
80
WT
Pla2
g7
KO
0
20
40
60
80
WT
Pla2
g7KO
0
50
100
150
200
250
WT
Pla2
g7KO
0
1
2
3
IL1
β (Fold)
*
WT
Pla2g
7KO
0
2
4
6
8
(^10) *
Adipose - 24 month old Adipose - 24 month old Adipose - 24 month old
F G H I
PLA2G7
NAC
C6
LPS
ProCasp1
Casp1
p20
p20
Casp1
PLA2G7
Flagellin
Poly(da:dT)
C6
LPS
ProCasp1
24 month old
pla2g7+/+
pla2g7-/-
L M
D
J
WT
Pla2g7
KO
0
5
10
15
20
40
60
80
100
TNFa (
pg/ml)
*
Procasp1
p20
actin
LPS - - + + + + + + + + + +
ATP MSU C6 NaArs Silica
WT KO WT KO WT KO WT KO WT KO WT KO
IL6 (
pg/ml)
IL1
β (
pg/ml)
Gro-alpha/KC (
pg/ml)
MCP1 (
pg/ml)
Eotaxin (
pg/ml)
PPAR
α (Fold)
Relative expression
IL1
β
Relative expression
Caspase 1
Relative expression
Ppar
α
Relative expression
Acvr1c
% of cells containing specks
E
Fig. 4. Inhibition of PLA2G7 protects against inflammaging and thymic
lipoatrophy(A) Circulating proinflammatory cytokines (TNF-a, IL-6, IL-1b,
Gro-alphaK/C, MCP-1, and Eotaxin) from serum in 24-month-old control and
Pla2g7–/–mice (B) qPCR analysis of relative expression ofIl-1bandPpara
compared withGapdhin sorted F4/80+cells from visceral adipose tissues in
24-month-old control and Pla2g7 KO mice and Caspase 1 protein expression in
the adipose tissue of 24-month-old control andPla2g7–/–deficient mice
(n= 3 and 3, respectively). (CandD) qPCR analysis of the proinflammatory
genesIl-1bandCasp1in the visceral adipose tissue of control and Pla2g7 KO
mice. (C and D) The CR-regulated fatty acid oxidation inducersPparaandAcvr1c
in subcutaneous adipose tissue (SAT) of 24-month-old control (C) and Pla2g7
KO mice (n= 5, 5) (D). (E) FACS analysis of proportions of different immune cell
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