The role of tumor suppressor factor CYLD in lung injury associated with acute necrotizing pancreatitis

Abstract

Objective Acute necrotizing pancreatitis (ANP) may cause lung injury.This study explores two factors that are associated with lung damage from ANP,the expression of tumor suppressor factor CYLD and nuclear factor-kappa B (NF-κB).Methods 72 adult Sprague-Dawley rats were randomly divided into 3 groups:sham operation,ANP,and GdCl3 treatment groups (n=24 for each group).A retrograde injection of 5％ sodium taurocholate into the biliopancreeatic duct of rats induced ANP,and the animals were killed 1,3,6,and 12 hours after the ANP induction.AMs were harvested by bronchoalveolar lavage technique,and TNF-a and IL-1β levels in bronchoalveolar lavage fluid (BALF) were evaluated.Lung tissue was checked with histological examinations,and the activity of NF-κB and CYLD in AM were measured by western blot.Results TNF-α and IL-1β secreted by AM were gradually elevated,peaked on the sixth hour,had maximums of (491.3 ±20.3)ng/L and (178.83±11.32)ng/L respectively,and decreased on the twelfth hour.The levels of TNF-α and IL-1β in the ANP group were significantly higher than the sham operation group (P＜0.05),and the GdC13 group levels were obviously lower than ANP group.In the sham operation group,the expression of NF-κB was low and CYLD was high.In the ANP group,when compared to the sham operation group,the expression of NF-κB rose after 3 hours and continued to rise with time progression (P＜0.05).In contrast,CYLD protein expression in the ANP group dropped after 3 hours and continued to gradually decrease (P＜0.05).The CYLD and NF-κB protein expression in GdCl3 groups had similar trends as the ANP group.GdCl3 group CYLD levels began to rise at 6 hours (P＜0.05),and NF κB levels began to fall at 1 hour (P＜0.05).The expression of NF-κB and CYLD possessed a negative correlation in both the ANP and GdCl3 groups (r =-0.918,r=-0.723,P＜ 0.01).Conclusions Therefore,in acute lung injury associated with acute pancreatitis,CYLD expression decreased with evident phases,such as a decrease in levels after 3 hours,and NF κB expression increased.Also,GdCl3 may be responsible for upregulation of CYLD expression and downregulation of NF-κB expression,and confirmed that CYLD had a negative effect on NF-κB.Perhaps GdCl3 could be used in the future to ameliorate the lung injury associated with ANP. Key words: Pancreatitis, acute necrotizing; Tumor suppressor proteins; Lung; Wounds and injuries