Transgenic expression of IL-33 activates CD8(+) T cells and NK cells and inhibits tumor growth and metastasis in mice.

Abstract

IL-33 is a multifunctional cytokine in immune regulation that activates Th1 cells, Th2 cells, CD8(+) T cells and NK cells. Our study showed that transgenic expression of IL-33 attenuated tumor metastasis in the B16 melanoma and Lewis lung carcinoma (LLC) metastatic models. The percentages and cytotoxicity of CD8(+) T cells and NK cells and their infiltration into the tumor tissues were significantly increased by the transgenic expression of IL-33 in tumor-bearing mice. Treatment with recombinant IL-33 could also increase the cytotoxicity of CD8(+) T cells and NK cells in vitro. In addition, depletion of CD8(+) T cells and NK cells using anti-CD8 or anti-asialo GM1 antibody abolished the pulmonary metastasis inhibition mediated by IL-33. Furthermore, IL-33 stimulated the activation of NF-κB and increased CD69 expression, which is a marker of the activated form of the two cell subsets, in CD8(+) T cells and NK cells. Our results suggest that IL-33 stimulated NF-κB signaling and promoted the proliferation, activation and infiltration of CD8(+) T cells and NK cells, which resulted in the inhibition of pulmonary metastasis in B16 melanoma and LLC mice models.

• Authors: Kun Gao, Xiaoying Li, Li Zhang, Lin Bai, Wei Dong, Kai Gao, Guiying Shi, Xianzhu Xia, Lingying Wu, Lianfeng Zhang
• Journal: Cancer letters (Cancer Lett) Vol. 335 Issue 2 Pg. 463-71 (Jul 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23499895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Il33 protein, mouse
• Interleukin-33
• Interleukins
• NF-kappa B

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Carcinoma, Lewis Lung (immunology, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Interleukin-33
• Interleukins (biosynthesis, genetics, metabolism)
• Killer Cells, Natural (immunology, metabolism)
• Lymphocyte Activation
• Melanoma, Experimental (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• NF-kappa B (immunology)
• Neoplasm Metastasis (genetics)