Expression of IL-32 modulates NF-kappa B and p38 MAP kinase pathways in human esophageal cancer

Background: Esophageal cancer is the seventh leading cause of cancer death in males in USA, and there is a strong link has been demonstrated between inflammation and esophageal cancer, interleukin (IL)-32 is a recently described pro-inflammatory cytokine characterized by the induction of nuclear factor NF-kappa B activation, the p38MAPK also plays an important role in key cellular processes related to inflammation and cancer. We investigated whether the IL-32 expression may be involved in esophageal carcinogenesis through modulates the activity of NF-kappa B and p-p38 MAPK. Method: Malignant esophageal tissue and blood samples were obtained from 65 operated untreated patients, normal samples was obtained from 35 patients operated for other reasons as control. IL-32 expression visualized by immunohistochemistry, Real time RT-PCR for IL-32 mRNA expression. NF-kappa B phosphorylation and phosphorylated p38mapk were analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines (TNF-alpha, IL-1 beta, IL-6 and IL-8) concentration in the patient's sera. Results: IL-32 expression was increased in immunohistochemical staining for malignant esophageal tissue and it's correlated with the relative expression level of IL-32 mRNA P = 0.007, the P-NF-kappa B level elevated in tumor tissue compared with control and no difference in the total NF-kappa B level P = 0.003 while the IL-32 up-regulated the P-pNF-kappa B in the esophageal tumor P = 0.005. There is increase in p-p38MAPK activation underlying IL-32 expression in tumor P = 0.004, but no change in total p38 MAPK in malignant esophagus. The plasma level of IL-32 expression was increased in malignant esophageal patients P = 0.01, with increased in the levels of the cytokines TNF-alpha, IL-6, and IL-1 beta P<0.05. Conclusions: Understanding the pathway of IL-32 expression to stimulate the secretion cytokines via the activation of NF-kappa B and up-regulation of p-p38MAPK may or may not prove to be a therapeutic target, or a biomarker, and future studies will finally answer this hypothesis generated. Published by Elsevier Ltd.