Interleukin-1β Stimulates the Proliferation of Cultured Airway Smooth Muscle Cells via Platelet-derived Growth Factor

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Abstract
Bronchoalveolar lavage fluid from symptomatic asthmatics contains elevated levels of several proinflammatory interleukins including interleukin-1 beta (IL-1 beta). Biologic activities of IL-1 beta are considered to be critical in the inflammatory process. Since these characteristics include mitogenic properties, we investigated the effect of IL-1 beta on the proliferation of airway smooth muscle (ASM) cells isolated from guinea pig tracheas. Primary tissue culture of ASM cells was maintained in media containing 0%, 1%, or 10% fetal bovine serum (FBS). Cultures were exposed up to 6 days to human recombinant IL-1 beta (20, 40, or 100 pg/ml) in the presence or absence of indomethacin. The proliferation of ASM cells was assessed with two techniques: a direct counting of cells with a hemocytometer and/or with a [3H]-thymidine incorporation, an established marker of DNA synthesis. The evaluation was done daily, up to the sixth day after exposure of cells to different doses of IL-1 beta. We found that the exposure of ASM cells to human recombinant IL-1 beta significantly (P < 0.01) increased the number of tracheal myocytes as well as the [3H]-thymidine incorporation into ASM cells. These changes were dependent upon the dose of IL-1 beta and the concentration of FBS in the cultured medium. The most active proliferation of ASM cells was observed in medium containing 1% FBS, indomethacin (1 microgram/ml), and IL-1 beta (100 pg/ml). The presence of indomethacin in the culture medium was essential to demonstrate the proliferative effect of IL-1 beta.(ABSTRACT TRUNCATED AT 250 WORDS)