Role of microtubules in LPS-induced macrophage inflammatory protein-2 production from rat pneumocytes.
We have recently demonstrated that primary cultured rat pneumocytes produce macrophage inflammatory protein-2 (MIP-2) in response to lipopolysaccharide (LPS) stimulation. In this study, we found that brefeldin A, by blocking anterograde transport from the endoplasmic reticulum (ER) to the Golgi apparatus, decreased LPS-induced MIP-2 in the culture medium and increased its storage in cells. This suggests that MIP-2 is secreted via a pathway from the ER to the Golgi apparatus, a process commonly regulated by microtubules. We further found that LPS induced depolymerization of microtubules as early as 1 min after LPS stimulation, and it lasted at least for 4 h. Preventing depolymerization of microtubules with paclitaxel (Taxol; 10 nM to 10 microM) partially inhibited LPS-induced MIP-2 production, whereas the microtubule-depolymerizing agents colchicine (1-10 microM) and nocodazole (1-100 microM) increased LPS-induced MIP-2 protein production without affecting MIP-2 mRNA expression. These results suggest that in pneumocytes, LPS-induced microtubule depolymerization is involved in LPS-induced MIP-2 production and that secretion of MIP-2 from pneumocytes is via the ER-Golgi pathway.
Isowa
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Thoracic Surgery Research Laboratory, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada M5G 2C4.
Keshavjee
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Liu
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006056:Golgi Apparatus / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000276:immunology*; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D020126:Brefeldin A; D017239:Paclitaxel; D015739:Nocodazole; D003078:Colchicine