Specific Inhibition of Cyclooxygenase 2 Restores Antitumor Reactivity by Altering the Balance of IL-10 and IL-12 Synthesis
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- Marina Stolina
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Sherven Sharma
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Ying Lin
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Mariam Dohadwala
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Brian Gardner
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Jie Luo
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Li Zhu
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Mitchell Kronenberg
- La Jolla Institute of Allergy and Immunology , San Diego, CA 92121
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- Patrice W Miller
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Joseph Portanova
- G. D. Searle , St. Louis, MO 63167
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- Jason C Lee
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
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- Steven M Dubinett
- UCLA-Wadsworth Pulmonary Laboratory , Los Angeles, CA 90073
書誌事項
- 公開日
- 2000-01-01
- 権利情報
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- https://academic.oup.com/pages/standard-publication-reuse-rights
- DOI
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- 10.4049/jimmunol.164.1.361
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Cyclooxygenase-2 (COX-2), the enzyme at the rate-limiting step of prostanoid production, has been found to be overexpressed in human lung cancer. To evaluate lung tumor COX-2 modulation of antitumor immunity, we studied the antitumor effect of specific genetic or pharmacological inhibition of COX-2 in a murine Lewis lung carcinoma (3LL) model. Inhibition of COX-2 led to marked lymphocytic infiltration of the tumor and reduced tumor growth. Treatment of mice with anti-PGE2 mAb replicated the growth reduction seen in tumor-bearing mice treated with COX-2 inhibitors. COX-2 inhibition was accompanied by a significant decrement in IL-10 and a concomitant restoration of IL-12 production by APCs. Because the COX-2 metabolite PGE2 is a potent inducer of IL-10, it was hypothesized that COX-2 inhibition led to antitumor responses by down-regulating production of this potent immunosuppressive cytokine. In support of this concept, transfer of IL-10 transgenic T lymphocytes that overexpress IL-10 under control of the IL-2 promoter reversed the COX-2 inhibitor-induced antitumor response. We conclude that abrogation of COX-2 expression promotes antitumor reactivity by restoring the balance of IL-10 and IL-12 in vivo.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 164 (1), 361-370, 2000-01-01
Oxford University Press (OUP)