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Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2017 Feb; Vol. 15 (2), pp. 805-812. Date of Electronic Publication: 2016 Dec 30. - Publication Year :
- 2017
-
Abstract
- Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the importance of the LPS/TLR4 interaction in apoptosis induced by oxidative stress in pancreatic β cells remains to be elucidated. The present study aimed to investigate the importance of TLR4 during LPS‑induced oxidative stress, apoptosis and dysfunction of insulin secretion in isolated islets of rats. LPS‑induced stimulation of TLR4 increased the production of reactive oxygen species and promoted apoptosis by upregulating the expression levels of caspase‑3, poly ADP ribose polymerase and altering the expression ratio of B‑cell lymphoma‑2 (Bcl‑2)/Bcl‑2 associated X protein. Additionally, the insulin secretion of islets cells was reduced. Anti‑TLR4 antibody and a knockdown of TLR4 by TLR4‑short hairpin RNA were used to inhibit TLR4 activity, which may reverse LPS‑induced events. The present study determined that in islets exposed to LPS oxidative stress, dysfunction may be partly mediated via the TLR4 pathway. Inhibition of TLR4 may prevent dysfunction of rat islets due to oxidative stress. The present study revealed that targeting the LPS/TLR4 signaling pathway and antioxidant therapy may be a novel treatment for the severely septic patients with hyperglycemia stress.
- Subjects :
- Animals
Caspase 3 metabolism
Cells, Cultured
Glucose pharmacology
Insulin metabolism
Islets of Langerhans cytology
Islets of Langerhans metabolism
Male
Microscopy, Fluorescence
Poly(ADP-ribose) Polymerases metabolism
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
RNA Interference
RNA, Messenger metabolism
RNA, Small Interfering metabolism
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Toll-Like Receptor 4 antagonists & inhibitors
Toll-Like Receptor 4 genetics
bcl-2-Associated X Protein genetics
bcl-2-Associated X Protein metabolism
Islets of Langerhans drug effects
Lipopolysaccharides toxicity
Oxidative Stress drug effects
Toll-Like Receptor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 28101570
- Full Text :
- https://doi.org/10.3892/mmr.2016.6097