@misc{oai:repo.qst.go.jp:00068709,
 author = {Akashi, Makoto and Watanabe, Keiko and Hachiya, Misao and 明石 真言 and 渡辺 恵子 and 蜂谷 みさを},
 month = {Apr},
 note = {The acute inflammatory response is accompanied by an increased number of granulocytes. However, granulocytes are short-lived cells in the circulation; they spontaneously undergo apoptosis.  The number of these cells is regulated by the balance of their production and elimination through apoptosis.  Since extremely rapid changes in the number of granulocyes have to be made in response to insults, other mechanisms than an enhanced production and maturation of these cells in the bone marrow are required.  OK342 is a heat- and penicillin-treated preparation of Streptococcus A3 and has anti-cancer activity; this agent is clinically used as an immuno-therapeutic agent in malignancies.  We studied the effect of OK432 on the apoptosis of human granulocytes induced by ultraviolet (UV)-radiation.  Flowcytometric analysis with the annexin-V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) showed that UV-radiation (0-200 mJ/cm2) induced apoptosis in a dose dependent manner.  Treatment of these cells with OK432 (0-0.5 KE/ml) inhibited UV-induced apoptosis.  Previous studies have shown that the extracellular signal-related protein kinase (ERK) pathway is involved in apoptosis of granulocytes.  To determine whether the ERK pathway is involved in the apoptosis of these cells, we used a specific inhibitor of MAPK kinase (MEK) inhibitor, PD98059.  Treatment of granulocytes with the inhibitor significantly inhibited apoptosis induced by UV-radiation.  On the other hand, OK432 activated ERK and inhibition of the ERK pathway by PD98059 blocked the anti-apoptotic effect of OK432.  Our findings suggest that the ERK pathway is involved in UV-induced apoptosis in granulocyes and that OK432 inhibits apoptosis by UV-radiation through a pathway requiring activation of ERK.  Exposure to UV-radiation on the skin induces skin cancer and also immuno-suppression.  OK432 is known to be an immuno-modulator.  Regulation of granulocyte survival may be one of the important mechanisms responsible for activities of OK432 in exposure to UV-radiation.},
 title = {Anti-cancer agent OK432 inhibits UV-induced apoptosis of human granulocytes},
 year = {2006}
}