Interleukin-1 beta stimulates the proliferation of cultured airway smooth muscle cells via platelet-derived growth factor.
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)
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J. B. Pierce Laboratory, New Haven, Connecticut 06519.
Zelazny
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Souhrada
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Souhrada
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D006168:Guinea Pigs; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D014132:Trachea / Q000166:cytology / Q000187:drug effects*
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor