Gadolinium chloride ameliorates acute lung injury associated with severe acute pancreatitis in rats by regulating CYLD/NF-κB signaling

• Published in: Biochemical and biophysical research communications 2017-10, Vol.492 (2), p.255-261
• Main Authors: Zhao, Xiuhao, Jin, Bei, Yang, Bin, Yan, Wenmao, Wu, Xianjia, Jiang, Cuinan, Cheng, Shi
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Acute Disease; Acute Lung Injury - complications; Acute Lung Injury - drug therapy; Acute Lung Injury - immunology; Acute Lung Injury - pathology; ANIMAL TISSUES; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; APOPTOSIS; Apoptosis - drug effects; CYLD; Cysteine Endopeptidases - immunology; DIGESTIVE SYSTEM DISEASES; GADOLINIUM; Gadolinium - pharmacology; Gadolinium - therapeutic use; Gadolinium chloride; GADOLINIUM CHLORIDES; INJURIES; Lung - drug effects; Lung - immunology; Lung - pathology; Lung injury; LUNGS; MACROPHAGES; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - immunology; Macrophages, Alveolar - pathology; Male; NF-kappa B; NF-kappa B - immunology; PANCREAS; Pancreas - drug effects; Pancreas - pathology; Pancreatitis - complications; Pancreatitis - drug therapy; Pancreatitis - immunology; Pancreatitis - pathology; PROTEINS; RATS; Rats, Sprague-Dawley; Severe acute pancreatitis; Signal Transduction - drug effects
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.08.061

The present study was embarked on an investigation of the mechanisms behind the effects of Gadolinium chloride (GdCl3) on lung injury associated with severe acute pancreatitis (SAP) in rats. Rats were randomly distributed into three groups: sham operation group (SO), SAP group and SAP treated with GdCl3 group (SAP + GdCl3). Retrograde injection of 5% sodium taurocholate into the biliopancreatic duct was adopted to induce SAP. Lung tissue specimens were harvested for histological study, wet-to-dry weight ratio calculation and myeloperoxidase examination. Meanwhile, bronchoalveolar lavage fluid was analyzed for TNF-α and IL-1β activity and proteins content. Then the apoptosis ratio of alveolar macrophages (AMs) was detected. NF-κB activation and cylindromatosis (CYLD) expression in AMs were measured respectively. Results showed that GdCl3 treatment notably ameliorated lung injury induced by SAP, and simultaneously, the apoptosis ratio of AMs was significantly promoted. The NF-κB activation was obviously inhibited when CYLD expression was markedly up-regulated in AMs of SAP + GdCl3. Negative correlation was analyzed between CYLD and NF-κB in both SAP and SAP + GdCl3. These data demonstrate that GdCl3 ameliorates lung injury secondary to SAP in rats mainly by up-regulating CYLD expression and inhibiting NF-κB activation in AMs, which may play a vital role in lung injury. •GdCl3 ameliorates lung injury associated with SAP by inducing the apoptosis of AMs.•NF-kB activation can inhibit the apoptosis of AMs.•CYLD negatively regulates NF-kB activation.