Activation and inactivation of cyclo-oxygenase in rat alveolar macrophages by aqueous cigarette tar extracts.
Cyclo-oxygenase (COX) activity and its level of expression, the release of arachidonic acid (AA), and the accumulation of prostaglandins (PGs) were determined in isolated rat pulmonary alveolar macrophages (PAM) exposed to aqueous cigarette tar (ACT) extracts. COX activity increased 3-fold above the initial activity within 2 h of incubation with ACT extracts and gradually decreased below the initial activity after 8 h of incubation. The increased COX activity after 2 h of incubation did not lead to increased accumulation of PGE2. Accumulated levels of PGE2 increased dramatically after 12 h of incubation despite decreased COX activity in cells incubated with ACT extracts. This increased accumulation of PGE2 was greater in cells derived from vitamin E deficient rats compared with control rats. Release of AA from cells was dramatically increased in cells incubated with ACT extracts in parallel to PG accumulation. Thus increased accumulation of PGE2 despite decreased COX activity after 12 h of incubation is likely the result of increased substrate availability. These results suggest that, contrary to earlier reports, cigarette smoke stimulates the formation of PGs in alveolar macrophages. Increased PG production may lead to suppressed immune response and enhanced risk of tumorigenesis in smokers' lungs.
Hwang
D
D
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA. hwangdh@mhs.pbrc.edu
Chanmugam
P
P
Boudreau
M
M
Sohn
K H
KH
Stone
K
K
Pryor
W A
WA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D010947:Plants, Toxic; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects; D013638:Tars / Q000494:pharmacology*; D014026:Nicotiana / Q000009:adverse effects; D014343:Trypan Blue; D014811:Vitamin E Deficiency / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D013638:Tars; C024746:tobacco tar; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D014343:Trypan Blue; D015232:Dinoprostone