title: Expression of IL-32 modulates NF-κB and p38 MAP kinase pathways in human esophageal cancer.
abstract: 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-κB 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-κB and p-p38 MAPK.
  
  
  METHODS
  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-κB phosphorylation and phosphorylated p38mapk were analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines (TNF-α, IL-1β, 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-κB level elevated in tumor tissue compared with control and no difference in the total NF-κB level P=0.003 while the IL-32 up-regulated the P-pNF-κB 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-α, IL-6, and IL-1βP<0.05.
  
  
  CONCLUSIONS
  Understanding the pathway of IL-32 expression to stimulate the secretion cytokines via the activation of NF-κB 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.
authors.affiliation: University of Colorado Denver, Department of Medicine and Surgery, 12700 E 19th Avenue, Aurora, CO 80045, USA. yousif_ghaly@yahoo.com
authors.forename: Nasser Ghaly
authors.initials: NG
authors.lastname: Yousif
authors.forename: Fadhil G
authors.initials: FG
authors.lastname: Al-Amran
authors.forename: Najah
authors.initials: N
authors.lastname: Hadi
authors.forename: Jillen
authors.initials: J
authors.lastname: Lee
authors.forename: Jonthan
authors.initials: J
authors.lastname: Adrienne
mesh_terms: D000368:Aged; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C496971:IL32 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases