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Table 1 Effect of PCI-32765 on monocytes, macrophages and mast cells

From: The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells

Cell type Stimulation EC 50 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         
  1. 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.