INH₂BP (5-iodo-6-amino-1,2-benzopyrone), a poly-ADP ribose polymerase inhibitor, has been shown to possess anti-cancer, anti-viral, and anti-inflammation properties. The aim of this study was to investigate the protective effect of INH₂BP against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells. While the treatment of H9c2 cardiomyoblasts cells with hydrogen peroxide (H₂O₂) caused a loss of cell viability and an increase in the number of apoptotic cells, INH₂BP significantly protected the cells against H₂O₂-induced cell death without any cytotoxicity. Our data also shows that INH₂BP significantly scavenged intracellular reactive oxygen species (ROS), and markedly enhanced the expression of antioxidant enzymes such as Mn-SOD (superoxide) and Cu/Zn-SOD, and heme oxygenase-1, which was accompanied by the concomitant activation of extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) phosphorylation in H9c2 cells. The effects of INH₂BP on ERK1/2 and p38 MAPK phosphorylation were abrogated by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. In addition, inhibition of ERK1/2 and p38 MAPK by these inhibitors significantly attenuated INH₂BP-mediated H9c2 viability as well as cleaved caspases-3, Bax, and Bcl-2 activation. Taken together, these results demonstrate that INH₂BP prevents H₂O₂-induced apoptosis in H9c2 cells by reducing the production of intracellular ROS, regulating apoptotic-related proteins, and the activation of the ERK1/2 and p38 MAPK.

It is generally accepted that ETAF/IL-1 is produced in epidermis by both keratinocytes and Langerhans' cells. We have studied the density and morphology of Ia+ epidermal dendritic cells in mice after systemic or intracutaneous injection of recombinant IL-1 beta. We found that rIL-1 beta decreased the density of Ia+ dendritic cells in the time period 2-7 days after rIL-1 beta administration. However, the remaining dendritic cells were enlarged and more arborized with increased expression of Ia antigen 1-4 days after injection of rIL-1 beta. The implication of the results is that ETAF/IL-1 modulates the function of Langerhans' cells through autocrine and paracrine regulation.

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