Hypothermia slows sequential and parallel steps initiated during caerulein pancreatitis

Vivek Mishra, Krutika Patel, Ram N. Trivedi, Pawan Noel, Chandra Durgampudi, Chathur Acharya, John A. Holmes, Sonya Narla, Vijay Prem Singh

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background and objectives: Multiple deleterious signaling cascades are simultaneously activated in acute pancreatitis (AP), which may limit the success of pharmacologic approaches targeting a single step. We explored whether cooling acinar cells slows distinct steps initiated from a stimulus causing pancreatitis simultaneously, and the temperature range over which inhibition of such deleterious signaling occurs. Methods: Caerulein (100 nM) induced trypsinogen activation (TGA), CXCL1, CXCL2 mRNA levels, cell injury were studied at 37°C, 34°C, 31°C, 29°C and 25°C in acinar cells. Trypsin, cathepsin B activities and cathepsin B mediated TGA were studied at 37°C, 23°C and 4°C. Results: There was >80% reduction in TGA, CXCL1 and CXCL2 mRNA levels at 29°C, and in cell injury at 34°C, compared to those at 37°C. Trypsin activity, cathepsin B activity and cathepsin B mediated TGA at 23°C were respectively, 53%, 64% and 26% of that at 37°C. Acinar cooling to 31°C reduced LDH leakage even when cooling was initiated an hour after caerulein stimulation at 37°C. Conclusions: Hypothermia synergistically and simultaneously slows parallel and distinct signaling steps initiated by caerulein, thereby reducing TGA, upregulation of inflammatory mediators and acinar injury.

Original languageEnglish (US)
Pages (from-to)459-464
Number of pages6
JournalPancreatology
Volume14
Issue number6
DOIs
StatePublished - 2014

Keywords

  • Acinar injury
  • Acute pancreatitis
  • Caerulein
  • Hypothermia
  • Inflammatory mediators
  • Trypsinogen activation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Hepatology

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    Mishra, V., Patel, K., Trivedi, R. N., Noel, P., Durgampudi, C., Acharya, C., Holmes, J. A., Narla, S., & Singh, V. P. (2014). Hypothermia slows sequential and parallel steps initiated during caerulein pancreatitis. Pancreatology, 14(6), 459-464. https://doi.org/10.1016/j.pan.2014.06.006