Table 1

Effect of PCI-32765 on monocytes, macrophages and mast cells

Cell type

Stimulation

EC50 in nM (peak concentration, pg/mL)


TNFα

IL-6

IL-1β

MCP-1

IL-8

Histamine

PGD2


THP-1

FcγR

LPS

0.9 (577)

> 10,000 (934)

ND

> 10,000 (638)

5.2 (80)

ND

ND

ND

Primary human monocytes

FcγR

LPS

2.6 (6854)

> 10,000 (2100)

3.9 (1380)

> 10,000 (528)

0.5 (100)

ND

908 (3593)

ND

Primary human macrophages

Primary mouse macrophages

FcγR

FcγR

561 (337)

4.9 (126)

1299 (1500)

0.9 (404)

26.6 (132)

5.1 (22)

422 (1451)

183 (676)

RAW 267.4

Primary human macrophages

FcγR (cFb)

FcγR (cFb)

8.7 (619)

113 (1350)

ND

ND

ND

ND

ND

ND

Human cultured mast cells

FcεR

FcγR

61 (236)

2.1 (67)

ND

ND

ND

ND

2.2 (341)

ND

32 (722)

7.7 (263)

25 (460*)

24 (238*)

21 (1573)

14 (575)

* ng/mL


PCI-32765 inhibits FcγR-stimulated production of TNFα, IL-6, IL-1β, and MCP-1 in THP-1 cells, human primary monocytes, human macrophages, and mouse macrophages. PCI-32765 inhibits human mast cell releases of histamine, PGD2, TNFα, IL-8, and MCP-1 following activations of FcεR and FcγR pathways. THP-1, primary monocytes, and monocyte-derived macrophages were stimulated with high concentration of plate-bound human IgG (or mouse IgG in case of mouse macrophages). RAW 267.4 cells and human macrophages were stimulated with plate-bound citrullinated fibrinogen immune-complexes (ICs) as described in Supplemental Methods [see Additional file 3]. Monocytes and macrophages were pre-treated with PCI-32765 for 30 minutes, and mast cells were treated for 10 minutes prior to stimulations. Mast cells were stimulated with anti-IgE or aggregated IgG1. The citrullinated fibrinogen IC experiments were performed twice in triplicates. All other experiments were performed three to five times in triplicate with similar results, and the average IC50 of two to three representative experiments is shown. Peak concentrations of readout cytokines/factors are in parenthesis. ND, no data.

Chang et al. Arthritis Research & Therapy 2011 13:R115   doi:10.1186/ar3400

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