Table 1

Target	Target Cell	Intervention	Main Result(s)	Reference
c-kit tyrosine kinase¹	Mast cells	Imatinib mesylate	↑ Apoptosis ↑ caspase-8,-9 ↓ TNF-α	116
ZAP-70²	B-cells	---	↑ Apoptosis in ZAP-70- B-cells	117
Telomerase	T-cells	---	↑ Apoptosis in T-cells with Telomerase insufficiency	118
NF-κB- inducible cytokines	T-cells	Bortezomib	↑ Apoptosis ↓ TNF-α, IL-1β, IL-6, IL-10	119
SIRT1³	RASF	TNF-α	↑ SIRT1 ↓ Apoptosis	120
PAR-2⁴	RASF	Tryptase	↑ Fas-mediated Apoptosis ↑ Rho kinase	121
Survivin	Monocytes	Survivin anti- sense oligonucleotides	↓ IL-6	122
NF-AT5⁵	RASF HUVEC⁶	NF-AT5 knock- down	↓proliferation/survival ↓angiogenic processes	123
Mcl-1⁷	FLS RASF	Mcl-2 anti-sense adenoviral vector EGCG⁸	↑ Apoptosis ↑ bax, bak, bim ↑ caspase-3 ↓Akt/NF-κB ↑survival/↑apoptosis	124 125
FasL	Synovial Fluid (SF) T- cells	CD7 fusion protein	↑ Apoptosis/RA and JIA SF T-cells; ↑ Fas- signaling in Th1, but not Th2 cells	126
Proinflammatory cytokines, E-selectin genes, adiponectin	MDC/PDC dendritic cells⁹	Berberine	↑ Apoptosis in MDC/PDC but not peritoneal macrophages, RAW 264.7 cells or Jurkat T- cells	127
STAT3, NF-κB (p65), bcl-2 in response to activation by IL-6/sIL6R FasL Geranylgeranyl phosphate	FLS JIA Monocytes RA Synoviocyte	Melittin Staurosporine Fluvastatin/ Pravastatin; GGTI-298¹¹ Y-27632¹²	↑ caspase-3,-9; ↑Apaf-1¹⁰, ↑ ↑cytosolic cytochrome c; ↓ p-STAT3, ↓p65 translocation, ↓ bcl-2, ↓ mitochondrial cytochrome c ↓ Apoptosis; ↓FasL Activation; ↓ Bid cleavage; ↓ Bcl-w ↑ Apoptosis by Fluvastatin and GGTI-298 ↔ Apoptosis by Pravastatin; ↑ Apoptosis by Y-27632	128 129 130

¹c-kit tyrosine kinase is a mast/tem cell growth factor receptor also known as CD117 [131]
² ZAP-70, ζ-chain-associated protein-70 and a member of the tyrosine kinase family that is normally expressed by T-cells and natural killer cells [132]
³SIRT1 is silent mating type information regulation 2 homolog (sirtuin-1) and a deacetylating enzyme [133]
⁴PAR-2, Protease-activated receptor-2 and a subfamily member related to G-protein coupled receptors that may be activated by cleavage through their extracellular domain [134]
⁵NF-AT5, Nuclear factor of activated T-cells 5 belonging to the NFAT family of transcription factors [135]
⁶Human umbilical vascular endothelial cells
⁷Mcl-1, Induced myeloid leukemia cell differentiation protein [136]
⁸ Epigallocatechin-3-gallate
⁹ MDC, myeloid-derived cells; PDC, plasmacytoid-derived cells
¹⁰ Apaf-1, Apoptotic protease activating factor-1
¹¹ An inhibitor of geranylgeranyl transferase [137]
¹² An inhibitor of RhoA kinase [138]

Table 1: Targets Relevant to Induction of Apoptosis in RA