IL-2 Induced Nitric Oxide Synthesis by Tumor Cells in Corultures of Lymphocytes and Tumor Cells.
- Author:
Chang Yeol YIM
1
;
Sang Youel PARK
;
Wan Hee YOO
;
Jae Yong KWAK
;
Soo Teik LEE
;
Myung Hee SOHN
;
Dae Ghon KIM
;
Deuk Soo AHN
Author Information
1. Department of Internal Medicine, Chonbuk National University, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
IL-2;
Nitric oxide;
Tumor;
Lymphocyte;
Arginine
- MeSH:
Animals;
Arginine;
Cell Culture Techniques;
Cell Proliferation;
Coculture Techniques;
Cytokines;
Interleukin-2*;
Lymphocytes*;
Mice;
Negotiating;
Nitric Oxide Synthase;
Nitric Oxide*
- From:Journal of the Korean Cancer Association
1999;31(2):339-347
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Nitric oxide (NO) synthesis has been known to be induced during interleukin-2 (IL-2) therapy. The present study was designed to elucidate mechanisms and roles of IL-2-induced NO synthesis in tumor cells. MATERIALS AND METHODS: Mechanisms of IL-2-induced NO synthesis were evaluated using in vitro culture systems of BALB/c mouse splenic lymphocytes and Meth-A tumor cells. Effects of IL-2-induced NO synthesis by Meth-A tumor cells on the tumor cell proliferation were also evaluated using an NO synthase inhibitor, N -monomethyl- L-arginine (MLA). RESULTS: Cultures of both lymphocytes alone and Meth-A tumor cells alone did not produce any significant amounts of nitrite, a stable metabolite of NO during IL-2 stimulation. In contrast, cocultures of lymphocytes and Meth-A tumor cells produced a large amount of nitrite during IL-2 stimulation. Addition of culture supernatants of lymphocytes incubated with IL-2 induced nitrite production in Meth-A tumor cell cultures. However, addition of culture supernatants of Meth-A tumor cells incubated with IL-2 did not induce nitrite production in lymphocyte cultures. Nitrite accumulation was markedly inhibited by addition of anti-interferon-y antibody, confirming the role of the cytokine in mediating tumor cell NO synthesis. MLA inhibited nitrite production by Meth-A tumor cells in a dose-dependent manner in the presence of culture supernatants of lymphocytes incubated with IL-2. Meth-A tumor cell nitrite production in the presence of increasing concentrations of MLA correlated inversely with tumor cell proliferation. CONCLUSION: NO synthesis can be induced by tumor cells by the secondarily released cytokines from lymphocytes during IL-2 stimulation. Autologous NO synthesized by tumor cells during IL-2 stimulation inhibits proliferation of tumor cells themselves.
