Glucocorticoid-Induced Attenuation of the Inflammatory Response in Zebrafish.

(1)

N o. of reg ula ted ge ne s

B

214 4

187 33 246

28 287

amp beclo

amp + beclo C

0

10

20

30

40

(2)

2 3 4 5

-5 -4 -3 -2 -1

2 3 4 5

-5 -4 -3 -2

Regulation by amputation Reg ul a tio n by a m pu ta tio n a nd be c lo m e tha s on e

Regulation attenuated

by beclomethasone

Regulation not attenuated

by beclomethasone

(3)

ccr12.2 mmp13a mmp9 il1b cd22 itln1 cxcl-c1c cd40 ch25h lygl1 il6st c6 anxa1a il12a ptgs2b irg1 alox5ap ncf2 ncf1 phf11 tnfrsf11b ptgis ptgfrn stam2 marco socs1a tnfrsf19 tlr4bb ifnphi1 tmed1b il17c

amp

beclo

amp + beclo

(4)

alox5ap

0 0.5 1 1.5 2 2.5

vehicle beclomethasone control amputation 0

0.5 1 1.5 2 2.5

vehicle beclomethasone control amputation

0 0.5 1 1.5 2 2.5

vehicle beclomethasone control amputation alox5a

lta4h Alox5ap

Alox5a/b1-3

Lta4h AA

5S-HpETE

LTA4

LTB4

m RN A c on c . (A U)

0 0.005 0.01 0.015

vehicle beclomethasone control amputation

C on c . (ng /m l)

LTB4

A

B

C

m RN A c on c . (A U) m RN A c on c . (A U)

D

E

Pro-inflammatory

(5)

AA

5S-HpETE

LTA4

LTB4

Alox12 Alox12b Alox15b

15S-HETE

LXA4 Alox5ap Alox5a/b1-3

0 0.05 0.1 0.15

vehicle beclomethasone control

amputation LXA4

C on c . (ng /m l)

0 0.5 1 1.5 2 2.5

vehicle beclomethasone control amputation

0 0.5 1 1.5 2 2.5

vehicle beclomethasone control amputation

0 0.5 1 1.5 2 2.5

vehicle beclomethasone control amputation alox12

alox15b alox12b

A

B

C

D

E

m RN A c on c . (A U) m RN A c on c . (A U) m RN A c on c . (A U)

Anti-inflammatory,

pro-resolving

(6)

CV

A

B

C

L-plastin: macrophages & neutrophils

Mpx: neutrophils

(7)

0 2 4 6 8 10 12 14

0 5 10 15 20 25

No. of m a c roph a ge s

Hours post amputation

DMSO Beclo

veh beclo

A

0 2 4 6 8 10 12 14

0 5 10 15 20 25

No. of ne utrop hi ls

Hours post amputation

DMSO Beclo

veh beclo

B

0 2 4 6 8 10 12 14

GR +/+ GR -/-

con beclo

gr

^s357

No. of ne utrop hi ls 4 h pa

veh beclo

C

*

Wild type

0 2 4 6 8 10 12 14

Macrophages Neutrophils

DMSO CHX

No. of c e ll s 4 hp a

veh chx

* *

D