SB202190

SB 202190 significantly inhibits both basal and anti-Fas antibody-induced MAPKAPK 2 activity in a dose-dependent manner. SB202190 by itself is sufficient to induce cell death in Jurkat and HeLa cells through activation of CPP32-like caspases, which can be blocked by expression of bcl-2. SB202190-induced apoptosis is attenuated by p38β but augmented by p38α. ^[2] SB 202190 strongly inhibits UVB induced COX-2 protein expression in HaCaT cells, and markedly inhibits UVB induced cox-2 mRNA. ^[3] SB 202190 treatment inhibits the expression of albumin-induced proinflammatory (monocyte chemoattractant protein-1) and transforming growth factor (TGF)-beta1-induced profibrotic (procollagen-Ialpha1) genes over 50% in renal tubular cells (normal rat kidney-52E). ^[4] SB 202190 treatment induces phosphorylation of JNK in a dose- and time- dependent manner in A549 cells, induces phosphorylation of ATF-2 transcription factor, and increases AP-1 DNA binding. ^[6] SB 202190 treatment enhances the growth of THP-1 and MV4-11 cells. SB 202190 increases the phosphorylation of c-Raf and ERK, suggesting that Ras-Raf-MEK-mitogen-activated protein kinase (MAPK) pathway activation is involved in the leukemia cell growth induced by SB 202190. ^[7]

Inhibiting p38 by administration of SB 202190 inhibits PV IgG-induced blister formation in the passive transfer mouse model. ^[5] In the endotoxin model of sepsis, SB 202190 treatment produces a statistically significant survival benefit compared with control. ^[8]

• In vitro kinase assays

  The p38α and p38β are assayed in 25 mM Tris-HCl, pH 7.5, containing 0.1 mM EGTA, with myelin basic protein (0.33 mg/mL) as substrate. Assays are performed either manually for 10 minutes at 30 °C in 50 μL incubations using [γ-³³P]ATP, or with a Biomek 2000 Laboratory Automation Workstation in a 96-well format for 40 minutes at ambient temperature in 25 μL incubations using [γ-³³P]ATP. The concentrations of ATP and magnesium acetate are 0.1 mM and 10 mM respectively. All assays are initiated with MgATP. Manual assays are terminated by spotting aliquots of incubation on to phosphocellulose paper, followed by immersion in 50 mM phosphoric acid. Robotic assays are terminated by the addition of 5 μL of 0.5 M phosphoric acid before spotting aliquots on to P30 filter mats. All papers are then washed four times in 50 mM phosphoric acid to remove ATP, once in acetone (manual incubations) or methanol (robotic incubations), and then dried and counted for radioactivity.

• Cell lines

  Jurkat, and HeLa

• Concentrations

  Dissolved in DMSO, final concentrations ~50 μM

• Incubation Time

  24 hours

• Method

  Cells are serum-starved and then treated with different concentration of SB 202190 for 24 hours. Cell viability is assayed by either trypan blue exclusion or propidium iodide exclusion followed by flow cytometry analysis. The apoptotic nuclei are visualized by H33258 staining.

• Animal Models

  C57BL/6J mice injected i.d. with a sterile solution of either control IgG or PV IgG

• Dosages

  12.5 μg

• Administration

  Administered via i.d.