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Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections.

ABSTRACT: Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidate the structures of four new host-protective molecules produced in neutrophil-endothelial cocultures and present in human and mouse tissues after sterile inflammation or infection. The bioactive molecules contain conjugated triene and diene double bonds, carry an alcohol at C13 and are derived from n-3 docosapentaenoic acid (DPA, C22:5). These compounds, termed 13-series resolvins (RvTs), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. RvTs also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2), increased by atorvastatin via S-nitrosylation of COX-2 and reduced by COX-2 inhibitors. The actions of atorvastatin and RvTs were additive in E. coli infections in mice, where they accelerated resolution of inflammation and increased survival >60%. Taken together, these results document host-protective molecules in bacterial infections, namely RvTs, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. These molecules regulate key innate protective responses in the resolution of infectious inflammation.

SUBMITTER: Dalli J

PROVIDER: S-EPMC4560998 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections.

Dalli Jesmond J Chiang Nan N Serhan Charles N CN

Nature medicine 20150803 9

Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidate the structures of four new host-protective molecules produced in neutrophil-endothelial cocultures and present in human and mouse tissues after sterile inflammation or infection. The bioactive molecules contain conjugated triene and diene double bonds, carry an alcohol at C13 and are derived from n-3 docosapentaenoic acid (DPA, C22:5). These compounds, t ...[more]

PMID: 26236990

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Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections.

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Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections.

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