Objective To investigate the expressions of ubiquitin-proteasome markers,including E2-14K,MAFbx,MuRF-1,and nuclear factor-κB(NF- κB) p50,in diaphragm of COPD rats,and their relationship with IL-17 level in diaphragm and serum in order to elucidate the potential mechanism of diaphragm atrophy.
Methods Thirty healthy adult male SD rats were randomly divided into a model group (n=18) and a normal control group (n=12). The COPD rat model was established by instillation of lipopolysaccharide (LPS) and exposure to cigarette smoke for 28 days. The protein levels of E2-14K,MAFbx,MuRF-1,and NF-κB p50 in diaphragm were measured by Western blot. The concentration of IL-17 in serum and diaphragm was measured by ELISA.
Results Western blot showed that the protein expressions of E2-14K,MAFbx,MuRF-1,and NF-κB p50 in diaphragm increased significantly in the COPD model group compared with the normal control group (0.96±0.12 vs. 0.53±0.09,0.99±0.10 vs. 0.53±0.08,0.95±0.08 vs. 0.51±0.16,1.11±0.10 vs. 0.64±0.50,respectively,P lt;0.01). The IL-17 level in serum and diaphragm was significantly higher in the COPD group than the control group. The expression of NF-κB p50 was positively correlated with E2-14K,MAFbx,and MuRF-1 expressions (r=0.82,0.92,0.86,respectively,P lt;0.01). Both in serum and diaphragm,IL-17 level was positively correlated with the percentage of neutrophils,levels of NF-κB p50,E2-14K,MAFbx,and MuRF-1 expressions(all P lt;0.01). The IL-17 levels in serum and diaphragm were also positively correlated each other (r=0.84,P lt;0.01).
Conclusions The results show that the ubiquitin-proteasom pathway,the NF-κB pathway and IL-17 are up-regulated in diaphragm of COPD rats .These alterations may contribute to diaphragm atrophy in COPD.
Citation: FAN Wei,LIU Zhaohui,ZHANG Xilin,LIANG Zhike,ZENG Xiangfu.. Atrophy Signaling in Diaphragm of COPD Rats and Relationship with IL-17. Chinese Journal of Respiratory and Critical Care Medicine, 2011, 10(6): 527-532. doi: Copy