Cathelicidin attenuates hyperoxia-induced intestinal injury through inhibition of NF-κB activity in newborn rats

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Abstract

Supplemental oxygen is often used to treat neonates with respiratory disorders. Preclinical studies have demonstrated that neonatal hyperoxia injures the distal small intestine and activates nuclear factor-κB (NF-κB). Cathelicidin inhibits NF-κB activity and ameliorates lipopolysaccharide-induced intestinal barrier disruption in rats. Sprague–Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O2) and were randomly treated with low-dose cathelicidin (4 mg/kg, LDC) and high-dose cathelicidin (HDC, 8 mg/kg) in 0.05 mL of normal saline (NS) administered intraperitoneally on postnatal days 1–6. The following six groups were obtained: RA + NS, RA + LDC, RA + HDC, O2 + NS, O2 + LDC, and O2 + HDC. The animals were sacrificed and the terminal ileum was removed for Western blot and histological analyses on postnatal day 7. The hyperoxia-reared rats exhibited significantly lower body weights, higher intestinal injury scores, lower occludin and ZO-1 expression, higher intestinal permeability and inducible IκB kinase inhibitor (IKKi) and NF-κB expression than the RA-reared rats. Cathelicidin treatment attenuated intestinal injury as evidenced by lower intestinal injury scores and intestinal permeability and higher intestinal barrier protein expression. The decrease in intestinal injury was accompanied by a decrease in IKKi and NF-κB. Cathelicidin attenuated hyperoxia-induced intestinal injury in the newborn rats, likely through NF-κB activity inhibition.

Original languageEnglish
Article number104269
JournalExperimental and Molecular Pathology
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Hyperoxia
Rats
Air
Wounds and Injuries
Permeability
Occludin
Ileum
Small Intestine
Lipopolysaccharides
Animals
Phosphotransferases
Western Blotting
Body Weight
CAP18 lipopolysaccharide-binding protein
Oxygen
Proteins

Keywords

  • Cathelicidin
  • Hyperoxia
  • Nuclear factor-κB
  • Occludin
  • ZO-1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

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title = "Cathelicidin attenuates hyperoxia-induced intestinal injury through inhibition of NF-κB activity in newborn rats",
abstract = "Supplemental oxygen is often used to treat neonates with respiratory disorders. Preclinical studies have demonstrated that neonatal hyperoxia injures the distal small intestine and activates nuclear factor-κB (NF-κB). Cathelicidin inhibits NF-κB activity and ameliorates lipopolysaccharide-induced intestinal barrier disruption in rats. Sprague–Dawley rat pups were reared in either room air (RA) or hyperoxia (85{\%} O2) and were randomly treated with low-dose cathelicidin (4 mg/kg, LDC) and high-dose cathelicidin (HDC, 8 mg/kg) in 0.05 mL of normal saline (NS) administered intraperitoneally on postnatal days 1–6. The following six groups were obtained: RA + NS, RA + LDC, RA + HDC, O2 + NS, O2 + LDC, and O2 + HDC. The animals were sacrificed and the terminal ileum was removed for Western blot and histological analyses on postnatal day 7. The hyperoxia-reared rats exhibited significantly lower body weights, higher intestinal injury scores, lower occludin and ZO-1 expression, higher intestinal permeability and inducible IκB kinase inhibitor (IKKi) and NF-κB expression than the RA-reared rats. Cathelicidin treatment attenuated intestinal injury as evidenced by lower intestinal injury scores and intestinal permeability and higher intestinal barrier protein expression. The decrease in intestinal injury was accompanied by a decrease in IKKi and NF-κB. Cathelicidin attenuated hyperoxia-induced intestinal injury in the newborn rats, likely through NF-κB activity inhibition.",
keywords = "Cathelicidin, Hyperoxia, Nuclear factor-κB, Occludin, ZO-1",
author = "Chou, {Hsiu Chu} and Chen, {Chung Ming}",
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AU - Chou, Hsiu Chu

AU - Chen, Chung Ming

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N2 - Supplemental oxygen is often used to treat neonates with respiratory disorders. Preclinical studies have demonstrated that neonatal hyperoxia injures the distal small intestine and activates nuclear factor-κB (NF-κB). Cathelicidin inhibits NF-κB activity and ameliorates lipopolysaccharide-induced intestinal barrier disruption in rats. Sprague–Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O2) and were randomly treated with low-dose cathelicidin (4 mg/kg, LDC) and high-dose cathelicidin (HDC, 8 mg/kg) in 0.05 mL of normal saline (NS) administered intraperitoneally on postnatal days 1–6. The following six groups were obtained: RA + NS, RA + LDC, RA + HDC, O2 + NS, O2 + LDC, and O2 + HDC. The animals were sacrificed and the terminal ileum was removed for Western blot and histological analyses on postnatal day 7. The hyperoxia-reared rats exhibited significantly lower body weights, higher intestinal injury scores, lower occludin and ZO-1 expression, higher intestinal permeability and inducible IκB kinase inhibitor (IKKi) and NF-κB expression than the RA-reared rats. Cathelicidin treatment attenuated intestinal injury as evidenced by lower intestinal injury scores and intestinal permeability and higher intestinal barrier protein expression. The decrease in intestinal injury was accompanied by a decrease in IKKi and NF-κB. Cathelicidin attenuated hyperoxia-induced intestinal injury in the newborn rats, likely through NF-κB activity inhibition.

AB - Supplemental oxygen is often used to treat neonates with respiratory disorders. Preclinical studies have demonstrated that neonatal hyperoxia injures the distal small intestine and activates nuclear factor-κB (NF-κB). Cathelicidin inhibits NF-κB activity and ameliorates lipopolysaccharide-induced intestinal barrier disruption in rats. Sprague–Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O2) and were randomly treated with low-dose cathelicidin (4 mg/kg, LDC) and high-dose cathelicidin (HDC, 8 mg/kg) in 0.05 mL of normal saline (NS) administered intraperitoneally on postnatal days 1–6. The following six groups were obtained: RA + NS, RA + LDC, RA + HDC, O2 + NS, O2 + LDC, and O2 + HDC. The animals were sacrificed and the terminal ileum was removed for Western blot and histological analyses on postnatal day 7. The hyperoxia-reared rats exhibited significantly lower body weights, higher intestinal injury scores, lower occludin and ZO-1 expression, higher intestinal permeability and inducible IκB kinase inhibitor (IKKi) and NF-κB expression than the RA-reared rats. Cathelicidin treatment attenuated intestinal injury as evidenced by lower intestinal injury scores and intestinal permeability and higher intestinal barrier protein expression. The decrease in intestinal injury was accompanied by a decrease in IKKi and NF-κB. Cathelicidin attenuated hyperoxia-induced intestinal injury in the newborn rats, likely through NF-κB activity inhibition.

KW - Cathelicidin

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