Celecoxib sensitizes Staphylococcus aureus to antibiotics in macrophages by modulating SIRT1.
Celecoxib sensitizes Staphylococcus aureus to antibiotics in macrophages by modulating SIRT1.
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DOI：
10.1371/journal.pone.0099285
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kalle AM
中科院分区：
文献类型：
--
作者：
Annamanedi M;Kalle AM
We have previously shown that celecoxib in combination with an antibiotic, increase the bacterial sensitivity to antibiotics. However, the underlying molecular mechanism remained elusive. Efficacy of the combinatorial treatment of celecoxib and ampicillin in vitro was evaluated on macrophage-phagocytosed S aureus. To elucidate the mechanism, signaling pathway of infection and inflammation involving TLR2, JNK, SIRT1 and NF-κB was studied by FACS, Western blot, ELISA and activity assays. Combinatorial treatment of ampicillin and celecoxib reduced the bacterial load in the macrophages. Further studies clearly suggested the activation of the master regulator of oxidative stress and inflammation SIRT1,, by celecoxib when used alone and/or in combination with ampicillin. Also, the results indicated that celecoxib inhibited JNK phosphorylation thereby stabilizing and activating SIRT1 protein that inhibited the COX-2 gene transcription with a significant decrease in the levels of protein inflammatory cytokines like IL-6, MIP-1α and IL-1β via inhibition of NF-κB. SIRT1 activation by celecoxib also resulted in increase of catalase and peroxidase activity with a decrease in Nitric oxide levels. In conclusion, we demonstrate a novel role of celecoxib in controlling inflammation as an enhancer of antibiotic activity against bacteria by modulating SIRT1.
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DOI：
10.1074/jbc.m110.198713
发表时间：
2011-04-01
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
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影响因子：
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发表时间：
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影响因子：
3.1
作者：
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影响因子：
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