Bradykinin stimulates interleukin-8 production by human lung fibroblasts

Bradykinin (BK) is a potent inflammatory mediator that is generated from kininogens by the actions of plasma and tissue kallikreins. Lung fibroblasts have the potential to participate in the inflammatory responses by releasing proinflammatory cytokines in response to a variety of stimuli. We postulated that human lung fibroblasts might produce interleukin-8 (IL-8) in response to BK stimulation. The present study showed that BK stimulated human lung fibroblasts to produce IL-8 in a dose- and time-dependent manner. Furthermore, Northern blot analysis showed that BK increased IL-8 mRNA expression. The stimulatory effect of BK on IL-8 production was detected at the concentration of 10 nm, and the maximal stimulation was achieved with 100 to 1000 nm. Phorbol 12-myristate 13-acetate pretreatment diminished the ability of BK to stimulate IL-8 production. In addition, GF109203X, a selective protein kinase C inhibitor, blocked BK-induced IL-8 production. These observations suggest that the stimulatory effect of BK on IL-8 production by lung fibroblasts is, at least partially, mediated through protein kinase C. These data suggest that BK may be involved in the inflammatory reaction leading to interstitial lung disorders through stimulating IL-8 production by lung fibroblasts.