Dietary advanced glycation end-products, its pulmonary receptor, and high mobility group box 1 in aspiration lung injury

Abstract

Background Gastric aspiration is a significant cause of acute lung injury and acute respiratory distress syndrome. Environmental risk factors, such as a diet high in pro-inflammatory advanced glycation end-products (AGEs), may render some patients more susceptible to lung injury after aspiration. We hypothesized that high dietary AGEs increase its pulmonary receptor, RAGE, producing an amplified pulmonary inflammatory response in the presence of high mobility group box 1 (HMGB1), a RAGE ligand and an endogenous signal of epithelial cell injury after aspiration. Materials and Methods CD-1 mice were fed either a low AGE (LAGE) or high AGE (HAGE) diet for 4 weeks. After aspiration injury with acidified small gastric particles, bronchial alveolar lavage (BAL) and whole-lung tissue samples were collected at 5 minutes, 1 hour, 5 hours, and 24 hours post-injury. RAGE, soluble RAGE (sRAGE), HMGB1, cytokine and chemokine concentrations, albumin levels, neutrophil influx, and lung myeloperoxidase (MPO) activity were measured. Results We observed that HAGE-fed mice exhibited greater pulmonary RAGE levels before aspiration and increased BAL sRAGE levels after aspiration compared to LAGE-fed mice. Lavage HMGB1 levels rose immediately after aspiration, peaking at 1 hour, and strongly correlated with sRAGE levels in both dietary groups. HAGE-fed mice demonstrated higher cytokine and chemokine levels with increased pulmonary MPO activity over 24 hours versus LAGE-fed mice. Conclusions This study indicates that high dietary AGEs can increase pulmonary RAGE, augmenting the inflammatory response to aspiration in the presence of endogenous damage signals such as HMGB1.

Kaempferol Improves Lung Ischemia-Reperfusion Injury via Antiinflammation and Antioxidative Stress Regulated by SIRT1/HMGB1/NF-κB Axis

“…HMGB1 is a highly conserved non-histone chromosome binding protein, which is closely related to a variety of lung diseases, including pneumonia (Tseng et al, 2014), tuberculosis (Zeng et al, 2015), chronic obstructive pulmonary disease (Sukkar et al, 2012), pulmonary fibrosis (Smit et al, 2014), and lung transplantation (Weber et al, 2014). Normally, HMGB1 is mainly concentrated in the nucleus.…”

Xuebijing Ameliorates Sepsis-Induced Lung Injury by Downregulating HMGB1 and RAGE Expressions in Mice

“…It has been demonstrated that increased production of proinflammatory cytokines and neutrophil accumulation could cause manifested inflammation, and Smit et al observed that upregulated HMGB1 induced these phenomena via activation of RAGE in aspiration lung injury [ 36 ]. Therefore, to assess whether XBJ treatment can reduce inflammatory cells counts and cytokines through reduced HMGB1 and RAGE expressions in the lung, differential cell counts and TNF- α , IL-1 β , and IL-6 levels were simultaneously investigated in the BAL fluids of the mice treated with or without XBJ at 6, 24, and 48 hours after CLP.…”

Emerging role of HMGB1 in lung diseases: friend or foe

“…PF is a respiratory disease caused by the scars formed in the lung tissues, leading to serious breathing problems. HMGB1 levels were significantly elevated in BALs or sputum in patients with PF [88]. Elevated sputum HMGB1 was correlated to 10% increased risk of lung function decline, whereas the increase in serum HMGB1 was associated with 5% increased risk of pulmonary disease progression [103].…”

“…In addition, red blood cell (RBC) transfusion could enhance the susceptibility to lung inflammation through released HMGB1 . Neutralizing anti‐HMGB1 monoclonal antibody conferred significant protection against PA‐induced neutrophil recruitment, bacterial infection and lung injury . In the presence of HMGB1, high dietary AGEs could increase RAGE expression to augment inflammatory response to aspiration .…”