The inflammatory cytokines tumor necrosis factor alpha and interleukin-1beta stimulate phosphatidylcholine secretion in primary cultures of rat type II pneumocytes.
Tumor necrosis factor alpha and interleukin-1beta increase surfactant secretion in type II pneumocytes in a time- and dose-dependent manner. This stimulatory effect was additive to that of lipopolysaccharide, suggesting that cytokines and lipopolysaccharide may exert their actions through different signal transduction pathways. Tumor necrosis factor alpha and interleukin-1beta did not modify the increase on phosphatidylcholine secretion induced by the direct protein kinase C activator tetradecanoylphorbol 13-acetate, whereas this effect was inhibited by the protein kinase C inhibitors bisindolylmaleimide (2 x 10(-6) M) and 1-(5-isoquinolinylsulphonyl)-2-methyl piperazone (10(-4) M). In addition, the stimulatory effect of tumor necrosis factor alpha and interleukin-1beta was not suppressed by the intracellular Ca2+ chelator BAPTA (5 x 10(-6) M) or by KN-62 (3 x 10(-5) M), a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results suggest that tumor necrosis factor alpha or interleukin-1beta stimulate phosphatidylcholine secretion via protein kinase C activation in a Ca2+-independent manner.
Benito
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Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Universidad Complutense, Madrid, Spain.
Bosch
M A
MA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D005434:Flow Cytometry; D007375:Interleukin-1 / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D004533:Egtazic Acid; D007770:L-Lactate Dehydrogenase; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium