Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model

Hiroyuki Itoh, Ito H, Toshihiro Sashihara, Akira Hosono, Shuichi Kaminogawa, Masayuki Uchida
Cytotechnology · 2011 · vol. 63(2) , pp. 133–141 · doi:10.1007/s10616-010-9321-x · PMID:21404062 · PMC3080483 · W2044663519
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Interleukin-12 suppressed endometriotic lesion development in mice by enhancing NK cell cytotoxicity, indicating NK cells are crucial for defense against ectopic endometrial tissue.

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This paper investigates whether peritoneal administration of interleukin-12 (IL-12) modulates the peritoneal immunosurveillance system, focusing on natural killer (NK) cells, in a murine endometriosis model. Mice challenged with ectopic endometrial tissue received IL-12 intraperitoneally for 5 consecutive days (day -2 to day 2), and the authors found increased cytotoxicity of splenic NK cells immediately after dosing and again on day 3, alongside reduced development of endometriotic lesions by day 21. In vivo NK function was probed by NK-related depletion using anti-IL-2Rβ monoclonal antibody, which reduced NK cytotoxicity and attenuated IL-12’s suppressive effect on lesion development. This paper is centrally about endometriosis—testing IL-12’s capacity to inhibit ectopic lesion development through NK cell activation in mice.

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Abstract

Involvement of impaired peritoneal immunosurveillance systems has been well established in the pathology of endometriosis. On the other hand, it has been observed that peritoneal administration of IL-12 suppress development of endometriotic lesions in a mouse endometriosis model. We investigated the effect of peritoneal administration of IL-12 on the peritoneal immunosurveillance system regarding NK cells in the mouse model. Treating the endometrial-tissue challenged mice with IL-12 for 5 consecutive days, from day -2 to day 2 (implantation of the endometrial tissues was done on day 0), cytotoxicity of splenic NK cells was enhanced immediately after the administration, on day 3, and development of the endometriotic lesions was reduced on day 21. In vivo NK cell depletion by administration of anti-IL-2Rβ mAb resulted in reduction of the cytotoxicity of splenic NK cells concomitant with a significant attenuation of suppressive effect of IL-12 on development of endometriotic lesions. Therefore, it was suggested that IL-12 suppresses development of endometriotic lesions via activation of NK cells, and that NK cells are involved in the primary defense for the development of endometriotic lesions. Similar content being viewed by others Abbreviations - IL: - Interleukin - INF: - Interferon - NK: - Natural killer

References

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J Exp Med 178:1103–1107 Weigent DA, Stanton GJ, Johnson HM (1983) Interleukin 2 enhances natural killer cell activity through induction of gamma interferon. Infect Immun 41:992–997 Acknowledgments We thank Satoh, Asako for technical supports and valuable suggestions. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Itoh, H., Sashihara, T., Hosono, A. et al. Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model. Cytotechnology 63, 133–141 (2011). https://doi.org/10.1007/s10616-010-9321-x Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10616-010-9321-x

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