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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Dalli J,Chiang N,Serhan CN

doi

10.1038/nm.3911

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

1071-5

issue

9

eissn

1078-8956

issn

1546-170X

pii

nm.3911

journal_volume

21

pub_type

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