Inflammatory stimuli promote oxidative stress in pancreatic acinar cells via Toll-like receptor 4/nuclear factor-κB pathway

Abstract

The Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway is vital to the pathogenesis of acute pancreatitis (AP). The aim of the present study was to identify the mechanism of the activation of the TLR4/NF-κB signaling pathway in the viability of primary pancreatic cells. The cells were stimulated with lipopolysaccharide (LPS) for the activation of NF-κB signaling. Next, the reactive oxygen species (ROS) level was evaluated by detecting the concentration of malondialdehyde and glutathione peroxidase. cell viability was measured by cell counting Kit-8 and MTT assays, while the percentage of apoptosis was detected by flow cytometry. Quantitative polymerase chain reaction was used to detect TLR4, B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax) and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) expression levels. Western blot assay was also conducted to detect TLR4 protein expression, while the activity of NF-κB signaling was measured by determining the p65 and phosphorylated p65 protein levels. In addition, the effect of TLR4 overexpression or treatment with TLR4 antagonists in the presence of LPS stimulation was investigated. The results revealed that ROS levels were increased and cell viability was decreased in LPS-stimulated pancreatic acinar cells. TLR4, Bax and PMAIP1 levels were increased, Bcl2 expression was decreased and NF-κB signaling was activated in LPS-stimulated pancreatic acinar cells. Furthermore, pancreatic cells with TLR4 overexpression exhibited increased ROS level and decreased viability. Finally, the effect caused by LPS stimulation was partially reversed by treatment of pancreatic acinar cells with TLR4 antagonists. In conclusion, the current study investigated a novel regulatory mechanism of the TLR4/NF-κB pathway in LPS-stimulated pancreatic cells, which may contribute to pancreatitis. The damage of these cells due to increased ROS levels was observed to occur through activation of the TLR4/NF-κB pathway.

The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms

“…The relation between oxidative stress status and nociception has been evident for decades [81][82][83][84][85]. Following inflammatory stimuli, the production of certain ROS (e.g., H 2 O 2 (hydrogen peroxides), 2O 2 − (superoxide), and ONOOH (peroxynitrite)) is increased to mediate various aspects of the immune response [86,87]. Moreover, oxidative mechanisms mediate thermal and mechanical hyperalgesia induced by nerve growth factor injections in both peripheral and central nerve fibers.…”

Protective effects of the notoginsenoside R1 on acute lung injury by regulating the miR-128-2-5p/Tollip signaling pathway in rats with severe acute pancreatitis

“…In acute pancreatitis, especially severe acute pancreatitis (SAP), the pancreatic cell injury is caused by abnormally activated pancreatic enzymes, activated monocyte macrophages, and a triggered cascade effect of pro-inflammatory cytokine synthesis and release. 1 The systemic inflammatory response syndrome occurs due to the aggravation of the pancreatic injury, resulting in injury, insufficiency, and even failure of the distal viscera. Acute lung injury (ALI) is one of the most common and severe complications of SAP.…”

“…Hypoxemia and acute respiratory distress syndrome (ARDS) are experienced by 30%–50% of patients with SAP. 1,3,4 Pulmonary lesions and functional changes often occur earlier in SAP than in organs (such as the heart, liver, and kidney) and are closely associated with early mortality in SAP. Thus, mortality reaches 60% in patients with SAP and pulmonary complications, such as ALI and ARDS.…”

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

“…Subsequently, the inflammation of the pancreas is initiated. Cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) as well as signaling molecules such as nuclear factor kappa-B (NF-κB) play an essential role in establishing the inflammatory response of AP (Gao et al 2020;Liu and Xia 2006;Pan et al 2018;Wu et al 2021). AP induces cell death through either apoptosis or necrosis according to the severity of the pancreatic injury as well as the species.…”