Abstract
Aspirin has been demonstrated to be effective in inhibiting COX-2 and PGE(2) in Alveolar macrophages (AMs). However, the mechanisms have not been fully understood. In the present study, we found that pretreatment with aspirin inhibited LPS-induced COX-2 and PGE(2) upregulation, IκBα degradation, NFκB activation and the increase of PKC activity, but elevated LPS-induced the decrease of PTP activity. The PKC inhibitor calphostin C dramatically reduced the COX-2 mRNA and PGE(2) levels, but the PTP inhibitor peroxovanadium (POV) significantly increased the COX-2 mRNA and PGE(2) levels. Furthermore, the PTP inhibitor mitigated the inhibitory effect of aspirin on COX-2 and PGE(2) upregulation and NF-κB activation, whereas the PKC inhibitor enhanced the inhibitory effects of aspirin on the production of COX-2 and PGE(2). Our data indicate a novel mechanism by which aspirin acts as a potent anti-inflammatory agent in alveolus macrophages and ALI.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Aspirin / pharmacology*
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism*
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Dinoprostone / metabolism*
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Hypoglycemic Agents / pharmacology
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I-kappa B Proteins / metabolism
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Lipopolysaccharides / toxicity
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Macrophages, Alveolar / drug effects*
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Macrophages, Alveolar / immunology
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Macrophages, Alveolar / metabolism
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Protein Tyrosine Phosphatases / metabolism*
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RNA, Messenger / metabolism
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Swine
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Up-Regulation / drug effects
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Vanadates / pharmacology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Hypoglycemic Agents
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I-kappa B Proteins
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Lipopolysaccharides
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NF-kappa B
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NFKBIA protein, human
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RNA, Messenger
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peroxovanadate
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NF-KappaB Inhibitor alpha
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Vanadates
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Cyclooxygenase 2
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PTGS2 protein, human
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Protein Kinase C
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Protein Tyrosine Phosphatases
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Dinoprostone
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Aspirin