INTERLEUKIN-8 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 PRODUCTION BY CULTURED HUMAN AIRWAY SMOOTH-MUSCLE CELLS

Leukocyte accumulation and activation are key events in the pathogenes is of inflammatory lung disease. The ability of human airway smooth mu scle cells (HASM) to contribute to the inflammatory process by its abi lity to produce the chemokines interleukin (IL) 8, monocyte chemotacti c protein (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES) was investigated. Cultured HASM, when stimulate d with the pro-inflammatory cytokines IL-1 alpha (0.01-1 ng/ml) or tum our necrosis factor alpha(TNF-alpha, 0.3-30ng/ml), synthesize and rele ase substantial amounts of IL-8, as assessed by specific immunoassay, bioasssay (elevation of intracellular free calcium in human nentrophil s), and upregulation of mRNA. These stimuli also increased MCP-1 produ ction and mRNA expression, but RANTES mRNA expression was not detected at 24 h. The smooth muscle spasmogen endothelin 1 (1 mu M) was unable to stimulate IL-8 or MCP-1 release or mRNA expression. These data ind icate that HASM may constitute an important source of leukocyte attrac tants in the inflamed lung, where the inducing stimuli, IL-1 alpha and TNF-alpha, are also likely to be present. (C) Academic Press Limited.