Bradykinin stimulates interleukin-8 production by human lung fibroblasts

Bradykinin (BK) is a potent in inflammatory mediator that is generated from kininogens by the actions of plasma and tissue kallikreins. Lung fibroblas ts have the potential to participate in the inflammatory responses by relea sing proinflammatory cytokines in response to a variety of stimuli. We post ulated that human lung fibroblasts might produce interleukin-8 (IL-8) in re sponse to BK stimulation. The present study showed that BK stimulated human lung fibroblasts to produce IL-8 in a dose- and time-dependent manner. Fur thermore, Northern blot analysis showed that BK increased IL-8 mRNA express ion. The stimulatory effect of BK on IL-8 production was detected at the co ncentration of 10 nM, and the maximal stimulation was achieved with 100 to 1000 nM. Phorbol 12-myristate 13-acetate pretreatment diminished the abilit y of BK to stimulate IL-8 production. In addition, GF109203X, a selective p rotein kinase C inhibitor, blocked BK-induced IL-8 production. These observ ations suggest that the stimulatory effect of BK on IL-8 production by lung fibroblasts is, at least partially, mediated through protein kinase C. The se data suggest that BK may be involved in the inflammatory reaction leadin g to interstitial lung disorders through stimulating IL-8 production by lun g fibroblasts.