Influence of Nuclear Factor kappaB Activation on Inflammatory Mediators of Alveolar Macrophages in Rats With Acute Necrotizing Pancreatitis.
Author(s): Sailai Y, Yu X, Baiheti P, Tang H, Li Y, Xu M
Affiliation(s): From the *Department of Emergent Surgery, First Teaching Hospital of Xinjiang Medical University, Xinjiang Province; and daggerDepartment of General Surgery, Third Xiangya Hospital, and double daggerLaboratory of Molecular Pharmacology, Xiangya College of Medicine, Central South University, Hunan Province, China.
Publication date & source: 2009-09-02, J Investig Med., [Epub ahead of print]
AIM:: To investigate the potential influence of nuclear factor kappaB (NF-kappaB) activation on the inflammatory mediators secreted by alveolar macrophages (AMs) in rats with acute necrotizing pancreatitis (ANP) and to evaluate the effect of an inhibitor of NF-kappaB-N-acetylcysteine (NAC). METHODS:: Ninety male Sprague-Dawley rats were randomly divided into 3 groups, 30 of each: control, ANP, and ANP plus NAC groups. The ANP rat models were established by a retrograde injection of 5% sodium taurocholate into the pancreatic duct. In addition to sodium taurocholate, the ANP plus NAC group received intravenous infusion of NAC (25 mg/100 g). At the sixth hour after modeling, the protein content of the bronchoalveolar lavage fluid, the myeloperoxidase in the lung tissue, and the transforming growth factor alpha and the nitric oxide (NO) secreted by AMs were determined. The histopathologic changes of the pancreas and the lung were observed under light microscope, and NF-kappaB activation of AMs was detected. RESULTS:: The protein content of the bronchoalveolar lavage fluid and the myeloperoxidase level of the lung tissue showed a significant increase in the ANP group as compared with the NAC-administered group. The levels of transforming growth factor alpha and NO secreted by AMs in the ANP and the ANP plus NAC group rose significantly over that in the control group, and there was a significant difference between them. Although they were still higher than those in the control group, the pancreas destruction and the lung injury were slighter in the ANP plus NAC group and the activation of NF-kappaB was lower in the ANP plus NAC group as compared with that in the ANP group. CONCLUSIONS:: The correlation between the NF-kappaB activation, the up-regulation of the inflammatory mediators secreted by AMs, and the tissue damage suggests a key influence of NF-kappaB in the pathogenesis of ANP. Inhibition of NF-kappaB activation may reverse the lung injury of ANP.