ENDOTHELIN-1 INDUCES CM-CSF, IL-6 AND IL-8 BUT NOT G-CSF RELEASE FROMA HUMAN BRONCHIAL EPITHELIAL-CELL LINE (BEAS-2B)

Endothelin (ET) is a powerful vasoconstrictor and bronchoconstrictor p eptide that may be involved in the pathogenesis of bronchial asthma. W e have investigated the effect of ET on the secretion of IL-6, IL-8, G M-CSF and G-CSF in a bronchial epithelial cell line (BEAS-2B), Incubat ion of BEAS-2B cells with ET-I (10(-13) to 10(-7) M) for 4 h caused do se-related increases in the release of IL-8 (68% increase above contro l, P < 0.001) and IL-6 (43% increase above control, P < 0.001), compar ed to untreated control cells. After 48 h incubation, ET-1 also increa sed the release of IL-8 by 35% (P < 0.001) and GM-CSF by 38% (P < 0.01 ). ET-1 had no significant effect on G-CSF release. ET-1 did not induc e cell proliferation at 24 or 48 h. Since ET-immunoreactive materials are expressed in epithelial cells in asthma, it is possible that ET-1 of epithelial origin may act in a paracrine or autocrine fashion on ai rway epithelial ET receptors to stimulate IL-8, IL-N6 and GM-CSF relea se, Thus, ET-1 may play a role in the regulation of the cytokine respo nses involved in inflammation of the airway mucosa.