EXPRESSION OF CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT IN RAT CARDIAC MYOCYTES

Accumulation and adhesion of leukocytes to cardiac myocytes play impor tant roles in the pathogenesis of inflammation-mediated myocardial inj ury such as ischaemia/reperfusion and myocarditis. The involvement of leukocyte chemotactic factors has been speculated in these processes. We investigated the expression of cytokine-induced neutrophil chemoatt ractant (CINC) in rat cardiac myocytes. CINC is a rat equivalent of hu man interleukin-8, On exposure to interleukin-1 alpha (IL-1 alpha), cu ltured neonatal rat cardiac myocytes released appreciable levels of CI NC both dose-and time-dependently. Tumor necrosis factor-alpha and lip opolysaccharide also significantly increased CINC accumulation in the culture supernatant, CINC mRNA expression was not observed in unstimul ated myocytes, however, the expression was markedly induced by exposur e to IL-1 alpha with a peak elevation at 3 h. Potent chemotactic activ ity for neutrophils was detected in the supernatant of cultured rat ca rdiac myocytes by stimulation with IL-1 alpha. This IL-1 alpha-induced chemotactic activity was significantly inhibited by polyclonal anti-C INC antiserum. Addition of dexamethasone, genistein, actinomycin D or cycloheximide significantly suppressed the IL-1 alpha-induced CINC acc umulation. Under hypoxia (95%N-2 + 5%CO2), CINC accumulation was incre ased in a time-dependent manner, and reoxygenation after hypoxia furth er intensified CINC accumulation. This hypoxia reoxygenation-induced C INC expression was significantly inhibited by pretreatment with dexame thasone. In conclusion, inflammatory stimuli induce the expression of CINC in rat cardiac myocytes, which may lead to myocardial injury via accumulation and activation of neutrophils. (C) 1995 Academic Press Li mited