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

Naomi Liza Denning, Weng Lang Yang, Laura Hansen, Jose Prince, Ping Wang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Introduction: Neonatal sepsis remains a leading cause of infant mortality. Cold-inducible RNA binding protein (CIRP) is an inflammatory mediator that induces TNF-α 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-1β, 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-1β 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 < 0.05; Max = 1). Apoptosis in the lungs, measured by TUNEL assay, was also decreased by 53% with C23 treatment (p < 0.05). Conclusions: Inhibition of CIRP with C23 treatment is protective in septic neonatal mice as demonstrated by reduced inflammatory markers systemically and in the lung. Therefore, C23 has promising therapeutic potential in treatment of neonatal sepsis. Level of evidence: Level I.

Original languageEnglish (US)
Pages (from-to)2053-2060
Number of pages8
JournalJournal of Pediatric Surgery
Volume54
Issue number10
DOIs
StatePublished - Oct 2019
Externally publishedYes

Keywords

  • CIRP
  • DAMPs
  • Inflammation
  • Lung injury
  • Neonatal sepsis

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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