Effects of gold sodium thiomalate and tenidap sodium (CP-66,248-2) on a model of macrophage differentiation using HL-60 cells.
We studied the effects of gold sodium thiomalate (GST) and a new antirheumatic drug, tenidap sodium ([Z]-5-chloro-2,3-dihydro-3-[hydroxy-2-thienylmethylene]-2-oxo-1H- indole-1-carboxamide, sodium salt), previously known as CP-66,248-2, in a model system of macrophage differentiation using a myelomonocytic cell line. HL-60 cells can be stimulated by vitamin D3 to differentiate along a monocytic pathway. Monocytic HL-60 cells express CD14 (Leu-M3), a macrophage surface marker, and develop the capacity to produce the second complement component (C2) in response to stimulation with cytokines such as gamma-interferon. The effects of GST and tenidap sodium were compared with the effects of dexamethasone and a variety of nonsteroidal antiinflammatory drugs in this model system. We found that GST inhibited the capacity of HL-60 cells to produce C2 but did not inhibit the expression of CD14. Tenidap sodium inhibited C2 production as well as CD14 expression, and it partially reversed the decrease in 3H-thymidine incorporation by HL-60 cells, which accompanies monocytic differentiation. At concentrations that inhibited C2 production by HL-60 cells, tenidap sodium did not inhibit C2 production by monocytes. Neither dexamethasone nor the other nonsteroidal antiinflammatory drugs tested possessed these activities. Thus, both GST and tenidap inhibit markers of monocytic differentiation in HL-60 cells, and this activity may relate to their antirheumatic activities.
Littman
B H
BH
McGuire Veterans Administration Medical Center, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Carlson
P L
PL
Loose
L D
LD
Sanders
K M
KM
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002762:Cholecalciferol / Q000494:pharmacology; D003175:Complement C2 / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors; D003907:Dexamethasone / Q000494:pharmacology; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000378:metabolism; D009288:Naproxen / Q000494:pharmacology; D000078183:Oxindoles; D013936:Thymidine / Q000378:metabolism
D003175:Complement C2; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D000078183:Oxindoles; D006052:Gold Sodium Thiomalate; D002762:Cholecalciferol; D009288:Naproxen; D003907:Dexamethasone; C062866:tenidap; D007930:Leucine; D013936:Thymidine