Molecular and histological evaluation of tumor necrosis factor-alpha expression in Helicobacter pylori-mediated gastric carcinogenesis.
OBJECTIVE
Helicobacter pylori (H. pylori) is considered to be a major factor contributing to gastric mucosal damage by stimulating mucosal macrophage production of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), but the inflammatory responses within the gastric mucosa in vivo are not well known. Therefore, this study was designed to investigate the expression of TNF-α induced by H. pylori infection which is involved in the tumor initiation and promotion of gastric carcinogenesis.


METHODS
This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status has been analyzed. The expression of TNF-α was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of TNF-α was also studied semiquantitatively by immunohistochemistry.


RESULTS
The RT-PCR and western blotting results of TNF-α mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of TNF-α in the similar way.


CONCLUSIONS
Over expression of TNF-α showed a significant severity-dose-response as risk markers from preneoplastic lesions to gastric cancer.
Senthilkumar
Cinghu
C
Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, Chennai, 600 025 Tamil Nadu, India.
Niranjali
Sivasithambaram
S
Jayanthi
Venkatraman
V
Ramesh
Thiyagarajan
T
Devaraj
Halagowder
H
D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism*; D005753:Gastric Mucosa / Q000276:immunology; D005756:Gastritis / Q000276:immunology; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D008679:Metaplasia; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000209:etiology; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha