W.-Y. Wang, Y. Chen, X. Su, D. Tang, Q.-W. Ben, W.-Y. Yao, P. Chen and Y.-Z. Yuan Pages 677 - 687 ( 11 )
Background: Resistin-like molecule-α (RELMα) has diverse regulatory functions in inflammation, but its role in severe acute pancreatitis (SAP) and acute pancreatitis associated lung injury (APALI) remains unclear.
Methods: SAP was induced in rats. RELMα protein expression was detected in lung tissue of rats to determine the relationship between APALI and RELMα. To investigate the effect of RELMα overexpression or knockdown on APALI, rats were given an intravenous injection of adenovirus vector before SAP induction. Lung and pancreatic samples were harvested 16 h after induction. After detection of RELMα protein levels, the severity of pancreatic and pulmonary injury was scored histologically, and serum and tissue levels of inflammatory mediators were measured. TUNEL assay and immunofluorescence were used to estimate pulmonary apoptosis and endothelial barrier integrity in lung tissue of SAP rats with RELMα knockdown.
Results: RELMα expression was significantly up-regulated in APALI and was related to the lung injury index. RELMα overexpression aggravated the release of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and serum C-reaction protein; the expression of inflammatory mediators phosphorylated (p)-AKT, p-P65, p-P38 mitogen activated protein kinase, p-extracellular regulated kinase, and intracellular adhesion molecule-1; and lung injury. RELMα knockdown had opposite effects. In addition, RELMα knockdown improved expression of proliferative cellular nuclear antigen, Bcl-2, zonal occluding-1 and Claudin-1 in lung tissue of SAP rats.
Conclusion: RELMα is associated with lung injury severity in SAP. RELMα augments inflammatory activity by increasing inflammatory cytokine release.
RELMα, severe acute pancreatitis, acute lung injury, pro-inflammatory, apoptosis, epithelial barrier.
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, 197 Ruijin Er Rd, Shanghai 200025, China.