Role of LPS-induced microfilament depolymerization in MIP-2 production from rat pneumocytes.
We have previously demonstrated that lipopolysaccharide (LPS) induces production of macrophage inflammatory protein-2 (MIP-2), a C-X-C chemokine for neutrophil recruitment and activation, in primary cultured rat lung alveolar epithelial cells. We have also demonstrated that LPS depolymerizes microfilaments in rat alveolar epithelial cells. To determine whether the polymerization status of microfilaments affects LPS-induced MIP-2 production, we treated rat alveolar epithelial cells with cytochalasin D (CytoD), a microfilament-disrupting agent, before and during LPS stimulation. A lower concentration (0.1 microM) of CytoD inhibited LPS-induced MIP-2 production without affecting microfilament polymerization. In contrast, LPS-induced MIP-2 production was enhanced by a higher concentration (10 microM) of CytoD, which disrupted the filamentous structure of actin. Jasplakinolide (1 nM to 1 microM), a polymerizing agent for microfilaments, decreased LPS-induced MIP-2 secretion. Jasplakinolide (1 microM) also blocked LPS-induced depolymerization of microfilaments. These results suggest that, in alveolar epithelial cells, LPS-induced MIP-2 production is at least partially regulated by microfilament depolymerization.
Thoracic Surgery Research Laboratory, Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada M5G 2C4.
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Isowa
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Liu
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015638:Cytochalasin D / Q000494:pharmacology; D047630:Depsipeptides; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D047630:Depsipeptides; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D011108:Polymers; C057531:jasplakinolide; D015638:Cytochalasin D