Neutrophil Gelatinase-Associated Lipocalin Protects Acinar Cells From Cerulein-Induced Damage During Acute Pancreatitis

Rakesh Bhatia, Sakthivel Muniyan, Christopher M. Thompson, Sukhwinder Kaur, Maneesh Jain, Rakesh K. Singh, Amaninder Dhaliwal, Jesse L. Cox, Shizuo Akira, Shailender Singh, Surinder K. Batra, Sushil Kumar

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: Elevated neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker for severe acute pancreatitis (SAP) and multiple organ failure, suggesting systemic and local contributions during pancreatitis. We investigated the role of NGAL locally on acinar cell biology. METHODS: Western blot, reverse transcriptase-polymerase chain reaction, and immunohistochemistry analysis were performed to analyze the levels of NGAL receptors, apoptotic and regeneration markers, and 4-hydroxynonenal (4HNE) levels, 3-[4,5-Dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide assay, and annexin V/propidium iodide staining were used to evaluate cell viability, and effect on endothelial cells was accessed by endothelial permeability assay. RESULTS: Cerulein treatment at 20 μM for 12 hours significantly reduced acinar cell viability by 40%, which was rescued by NGAL at 800 and 1600 ng/mL concentrations, observed during mild and SAP, respectively. Mechanistically, NGAL significantly reduced the levels of reactive oxygen species and 4HNE adduct formation in a 24p3R-dependent manner and upregulated the expression of acinar cell regeneration markers, like CDK-2, CDK-4, and C-myc. However, SAP levels of NGAL significantly increased endothelial permeability and downregulated the levels of ZO-1, and cerulein treatment in NGAL knockout mice showed increased levels of 4HNE adducts. CONCLUSIONS: Neutrophil gelatinase-associated lipocalin rescues intracellular reactive oxygen species during pancreatitis and promotes survival and regeneration of acinar cells.

Original languageEnglish (US)
Pages (from-to)1297-1306
Number of pages10
JournalPancreas
Volume49
Issue number10
DOIs
StatePublished - Nov 1 2020

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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