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 language | English |
|---|---|
| Pages (from-to) | 2902-2908 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 163 |
| Issue number | 5 |
| Publication status | Published - 1999 Sep 1 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
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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 journal › Article
TY - JOUR
T1 - A novel function of IL-12p40 as a chemotactic molecule for macrophages
AU - Ha, Sang-Jun
AU - Lee, Chu Hee
AU - Lee, Seong Beom
AU - Kim, Chang Min
AU - Jang, Kyung Lib
AU - Shin, Hee Sup
AU - Sung, Young Chul
AU - Sung, Young Chul
PY - 1999/9/1
Y1 - 1999/9/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0000155803&partnerID=8YFLogxK
M3 - Article
C2 - 10453037
AN - SCOPUS:0000155803
VL - 163
SP - 2902
EP - 2908
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -