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C23, an oligopeptide derived from cold-inducible RNA-binding protein, suppresses inflammation and reduces lung injury in neonatal sepsis.


ABSTRACT: INTRODUCTION:Neonatal sepsis remains a leading cause of infant mortality. Cold-inducible RNA binding protein (CIRP) is an inflammatory mediator that induces TNF-? production in macrophages. C23 is a CIRP-derived peptide that blocks CIRP from binding its receptor. We therefore hypothesized that treatment with C23 reduces systemic inflammation and protects the lungs in neonatal sepsis. METHODS:Sepsis was induced in C56BL/6 mouse pups (5-7?days) by intraperitoneal injection of adult cecal slurry (0.525?mg/g body weight, LD100). One hour later pups received retroorbital injection of C23 (8?mg/kg) or vehicle (normal saline). Ten hours after sepsis induction, blood and tissues were collected for analysis. RESULTS:C23 treatment resulted in a 58% and 69% reduction in serum levels of proinflammatory cytokines IL-6 and IL-1?, respectively, and a 40% and 45% reduction of AST and LDH, as compared to vehicle-treated septic pups. In the lungs, C23 treatment reduced expression of cytokines IL-6 and IL-1? by 78% and 74%. In addition, the mRNA level of neutrophil chemoattractants KC and MIP-2 was reduced by 84% and 74%, respectively. These results corresponded to a reduction in histologic lung injury score. Vehicle-treated pups scored 0.49?±?0.19, while C23 treatment reduced scores to 0.29?±?0.12 (p?

SUBMITTER: Denning NL 

PROVIDER: S-EPMC6609502 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

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