Interferon-gamma regulates apoptosis by releasing soluble tumor necrosis factor receptors in a gastric epithelial cell line.
OBJECTIVE
Interferon (IFN)-gamma and tumor necrosis factor (TNF) are predominant cytokines produced in the gastric mucosa of patients with Helicobacter pylori-infected gastritis. Several studies reported that IFN-gamma and TNF induced the synergistic effect on many cell lines. We attempted to clarify the apoptotic activity and the synergistic effect of IFN-gamma and TNF on the gastric epithelial cell, and whether IFN-gamma relates to soluble TNF receptors (sTNF-R) release from the gastric epithelial cell.


METHODS
On the gastric epithelial cell line MKN45, cytotoxic and apoptotic effects of IFN-gamma and TNF were examined. Next, sTNF-R released in response to IFN-gamma and the protective effect of sTNF-R against the cytotoxic activity of TNF and IFN-gamma were examined by blocking the release of sTNF-R with a serine protease inhibitor such as phenylmethylsulfonyl fluoride.


RESULTS
Interferon-gamma significantly decreased cell viability, but TNF decreased it only slightly. Interferon-gamma and TNF did not make a synergistic effect on cell viability and apoptosis. Interferon-gamma and TNF induced sTNF-R release from gastric epithelial cells. Phenylmethylsulfonyl fluoride significantly inhibited shedding of sTNF-R and a synergistic effect of TNF and IFN-gamma on apoptosis was observed.


CONCLUSIONS
These results suggest that sTNF-R released by IFN-gamma regulate the injury on the gastric epithelial cell line induced by TNF.
Furuta
Shimako
S
Second Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Japan. shimako@ff.iij4u.or.jp
Goto
Hidemi
H
Niwa
Yasumasa
Y
Ohmiya
Naoki
N
Kamiya
Kenji
K
Oguri
Akihiko
A
Hayakawa
Tetsuo
T
Mori
Naoyoshi
N
D017209:Apoptosis; D002460:Cell Line; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D018124:Receptors, Tumor Necrosis Factor; D010664:Phenylmethylsulfonyl Fluoride; D007371:Interferon-gamma