Table 3 Inhibition of nigericin and ATP-induced IL-1β release from post-differentiated THP1 cells and primary cultured neonatal microglia.

From: Development of a characterised tool kit for the interrogation of NLRP3 inflammasome-dependent responses

Drug

Nigericin-induced IL-1β release from post-differentiated THP1 cells

Nigericin-induced IL-1β release from neonatal microglia

ATP-induced IL-1β release from neonatal microglia

P2X7 antagonists

pIC 50

IC 50 (µM)

pIC 50

IC 50 (μM)

pIC 50

IC 50 (μM)

CE-224,535

—

—

—

—

6.18

0.66

AZD9056

—

—

—

—

7.52

0.03

25 (from19)

—

—

—

—

7

0.1

26 (from19)

—

—

—

—

7.52

0.03

Diarylsulfonylurea inflammasome inhibitor series

Glyburide

6

1.12

4.68

20.81

4.57

26.86

CP-412,245

7.3

0.06

6.51

0.31

6.85

0.14

CP-424,174

7.9

0.01

6.51

0.31

6.92

0.12

CRID1

7.6

0.03

6.72

0.19

6.8

0.16

CRID2

8

0.01

6.74

0.18

6.66

0.22

MCC950

8.5

0.004

7

0.1

7.22

0.06

NBC inflammasome inhibitor series

NBC6

5.2

6.3

5.96

1.17

5.33

4.67

NBC11

5.8

1.66

5.84

1.44

5.53

2.93

NBC12

6.3

0.48

6

0.99

5.53

2.98

NBC13

6.4

0.41

6.06

0.87

5.69

2.02

NBC19

7.1

0.08

5.93

1.18

6.07

0.85

Caspase-1 inhibitor

      

VX-765

7.8

0.01

7.15

0.07

7.3

0.05

  1. THP1 cells were primed with 1 µg/ml LPS overnight, treated with inhibitors for 30 minutes and further stimulated with nigericin (10 µM, 1 h). ASC specks were analysed (Table 2) and supernatants used for MSD quantification of IL-1β release. pIC50 and IC50 values were determined by normalisation to vehicle-treated controls, and obtained from at least 3 independent experiments. Assays were performed using microglial cultures primed with LPS (1 μg/ml, 3 h), treated 15 minutes with the inhibitors, and further activated with ATP (5 mM, 1 h) or nigericin (10 μM, 1 h). pIC50 and IC50 values were determined by vehicle-normalised ELISA quantification of IL-1β, and obtained from at least 3 independent cultures (litters).
Back to article page