Title:High-Dose Linoleic Acid Activated JAK2-STAT3 Signaling Pathway Involved in Cytokine Production and Lipogenesis in Pancreatic Exocrine Cells
Volume: 16
Issue: 7
Author(s): F. Zhu, Y. Guan and R. Zhang
Affiliation:
Keywords:
JAK2, STAT3, linoleic acid, cytokines, fatty acid synthase.
Abstract: Background: Linoleic acid has been implicated in the
pathogenesis of acute pancreatitis. However, molecular mechanisms
underlying adverse effects of large-dose linoleic acid remain unclear.
Current study aimed to explore the impact of high-dose linoleic acid on the
activation of Janus kinase 2 (JAK2)-signal transducers and activators of
transcription 3 (STAT3) pathway, cytokine production, and lipogenesis in
pancreatic exocrine cells.
Methods: MTT assay was used to detect the viability of AR42J rat
pancreatic exocrine cells, and lactate dehydrogenase assay was utilized to
detect cytotoxicity. Concentrations of interleukin (IL)-6 and tumor necrosis
factor (TNF)-α were detected by ELISA, and protein expression of JAK2, p-JAK2, STAT3, p-
STAT3, and fatty acid synthase (FAS) was examined by Western Blot. The impact of highdose
linoleic acid on JAK2-STAT3 pathway was also examined when JAK2 was inhibited by
AG490, and STAT3 expression was interrupted by siRNA.
Results: The cell viability of AR42J rat pancreatic exocrine cells was inhibited, and
cytotoxicity was increased by high-dose linoleic acid. JAK2 and STAT3 proteins in pancreatic
exocrine cells were activated by high-dose linoleic acid via phosphorylation and nuclear
localization of phosphorylated STAT3. Moreover, the expression of downstream proteins in
JAK2-STAT3 pathway (IL-6, TNF-α and FAS) was up-regulated by high-dose linoleic acid.
The increased levels of IL-6 and TNF-α caused by high-dose linoleic acid were attenuated by
JAK2 inhibitor AG490. p-JAK2 protein was up-regulated, whereas p-STAT3, STAT3 and FAS
proteins were down-regulated by high-dose linoleic acid in the presence of STAT3-siRNA.
Conclusion: The cytotoxicity was increased and JAK2-STAT3 signaling pathway was
activated by high-dose linoleic acid through cytokine production and lipogenesis in rat
pancreatic exocrine cells.
