Antisense oligodeoxynucleotide studies with

Previous studies have reported that ERKs are characteristically associated with cell proliferation and protection from apoptosis (Bl, XI), while activation of JNK and p38 MAPK can promote apoptosis in many systems, including B lymphocytes (G5), cerebellar granule cells (K3), hematopoietic cells (K8), and neuronal cells (M3, XI). On the other hand, a recent report found that a pyridinyl imidazole, SB 202190, the specific inhibitor of p38 MAPK, by itself was sufficient to induce apoptosis in T lymphocyte Jurkat cells (N2). Moreover, Th-2-derived cytokine IL-5, the ERK activator and antiapoptotic factor for eosinophils, could also activate p38 MAPK in human eosinophils (BIO). We recently reported that cytokine IL-3, IL-5, and GM-CSF could prolong survival of human eosinophilic leukemic (EoL-1) cells through the transient activation of ERK (W15). On the other hand, activation of p38 MAPK in EoL-1 cells by the NSAID sodium salicylate (NaSal) could lead to apoptosis (W15). We also found that the suppression of ERK using ERK antisense phosphorothioate oligodeoxynucleotides could promote the apoptosis of peripheral blood eosinophils (W16). Moreover, we found that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK activity in eosinophils are regulated by caspases (Z2). 

Complement Activation. With 2-h infusions at a dose of 2 mg/kg, no increases in complement-split products were observed in more than 300 patients with inflammatory diseases treated with ISIS 2302, a 20-nucleotide phosphorothioate antisense inhibitor of ICAM-1. Similarly, ISIS 5132, an inhibitor of C-raf kinase was dosed from 0.5 to 6.0 mg/kg and no meaningful increases in complement-split products were observed. ISIS 3521, a PKCa inhibitor gave equivalent data and both of these drugs were studied in patients with various malignant diseases. Similar data were observed with all the phosphorothioate oligodeoxynucleotides administered on this... 

---