Science - USA (2022-02-11)

(Antfer) #1

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

RESEARCH | REPORTS

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