A novel function of IL-12p40 as a chemotactic molecule for macrophages

Sang-Jun Ha, Chu Hee Lee, Seong Beom Lee, Chang Min Kim, Kyung Lib Jang, Hee Sup Shin, Young Chul Sung, Young Chul Sung

Research output: Contribution to journalArticle

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Abstract

IL-12p70 plays a pivotal role in regulating the Th1/Th2 balance in the initial stage of immune responses. In contrast, IL-12p40, which is produced excess over IL-12p70, has been known to down-regulate IL-12p70-mediated responses by acting as an antagonist. To investigate in vivo function of IL- 12p40, RH7777 rat hepatoma cells were engineered to inducibly express mouse IL-12p40 under the tight control of doxycycline (dox). In the absence of dox, s.c. injection of these cells into syngeneic rat was shown to generate tumors. However, the induction of IL-12p40 by dox was sufficient for inhibiting tumor formation, as well as for tumor regression. Immunohistochemical analysis showed that macrophages, but not CD4 + T, CD8 + T, and NK cells, were predominantly recruited into tumor sites as early as 3 days after IL-12p40 induction. These results were further supported by the observation that IL-12p40, but not C-terminal deletion mutants by more than 5 amino acids, was able to chemoattract peritoneal macrophages in vitro, suggesting that IL-12p40, when produced in a large excess over IL-12p70 in vivo, can initially amplify the immune responses against tumors by directly recruiting macrophages. Our findings indicate that IL-12p40 may function as an effector molecule as well as an antagonist of IL-12p70.

Original languageEnglish
Pages (from-to)2902-2908
Number of pages7
JournalJournal of Immunology
Volume163
Issue number5
Publication statusPublished - 1999 Sep 1

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Interleukin-12 Subunit p40
Macrophages
Doxycycline
Neoplasms
Th1-Th2 Balance
Peritoneal Macrophages
Natural Killer Cells
Hepatocellular Carcinoma
Down-Regulation
T-Lymphocytes
Amino Acids
Injections

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ha, S-J., Lee, C. H., Lee, S. B., Kim, C. M., Jang, K. L., Shin, H. S., ... Sung, Y. C. (1999). A novel function of IL-12p40 as a chemotactic molecule for macrophages. Journal of Immunology, 163(5), 2902-2908.
Ha, Sang-Jun ; Lee, Chu Hee ; Lee, Seong Beom ; Kim, Chang Min ; Jang, Kyung Lib ; Shin, Hee Sup ; Sung, Young Chul ; Sung, Young Chul. / A novel function of IL-12p40 as a chemotactic molecule for macrophages. In: Journal of Immunology. 1999 ; Vol. 163, No. 5. pp. 2902-2908.
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Ha, S-J, Lee, CH, Lee, SB, Kim, CM, Jang, KL, Shin, HS, Sung, YC & Sung, YC 1999, 'A novel function of IL-12p40 as a chemotactic molecule for macrophages', Journal of Immunology, vol. 163, no. 5, pp. 2902-2908.

A novel function of IL-12p40 as a chemotactic molecule for macrophages. / Ha, Sang-Jun; Lee, Chu Hee; Lee, Seong Beom; Kim, Chang Min; Jang, Kyung Lib; Shin, Hee Sup; Sung, Young Chul; Sung, Young Chul.

In: Journal of Immunology, Vol. 163, No. 5, 01.09.1999, p. 2902-2908.

Research output: Contribution to journalArticle

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Ha S-J, Lee CH, Lee SB, Kim CM, Jang KL, Shin HS et al. A novel function of IL-12p40 as a chemotactic molecule for macrophages. Journal of Immunology. 1999 Sep 1;163(5):2902-2908.