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Park, Lee, Yim, Yang, Yoo, Lee, Han, Shim, and Kim: Expression of COX-2 and IDO by Uteroglobin Transduction in NSCLC Cell Lines
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2009; 66(4): 274-279.

Published online: 30 April 2009

DOI: https://doi.org/10.4046/trd.2009.66.4.274

Expression of COX-2 and IDO by Uteroglobin Transduction in NSCLC Cell Lines

Gun Min Park, M.D.1, Sang-Min Lee, M.D.2, Jae-Joon Yim, M.D.2, Seok-Chul Yang, M.D.2, Chul Gyu Yoo, M.D.2, Choon-Taek Lee, M.D.3, Sung Koo Han, M.D.2, Young-Soo Shim, M.D.2, Young Whan Kim, M.D.2

1Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Gyeongju, Korea.

2Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.

3Respiratory Center, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Address for correspondence: Young Whan Kim, M.D. Department of Internal Medicine, Seoul National University College of Medicine, 28, Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea. Phone: 82-2-2072-2856, Fax: 82-2-762-9662, ywkim@snu.ac.kr

Received 11 February 2009       Accepted 18 March 2009

Copyright©2009. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Abstract

Background

Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO.

Methods

In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549.

Results

Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-γ) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-γ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2.

Conclusion

The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.

Keywords: Uteroglobin, Cyclooxygenase 2, Indoleamine 2,3-dioxygenase, Interferon-gamma, Immune tolerance

Figures and Tables

Figure 1
Expression of COX-2 and IDO in NSCLC cell lines transduced with Uteroglobin (UG). (A) Both COX-2 and IDO were expressed in A549 and H460 cells. Transduction of Ad-UG (20 moi) directly to A549 and H460 cells decreased expression of both COX-2 and IDO. (B) COX-2 was expressed in H157 cells. Transduction of Ad-UG (20 moi) directly to H157 cells decreased expression of COX-2. But, IDO was not expressed in H157 cells.
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Figure 2
Change of expression of COX-2 and IDO after UG transduction, instillation of IFN-γ, UG transduction after instillation of IFN-γ and instillation of IFN-γ after UG transduction, in A549, non-small cell lung cancer cell line.
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Figure 3
Expression of COX-2 and IDO in A549 cell line transduced with Uteroglobin (UG) as transfection with COX-2 sense or siRNA. (A) COX-2 and IDO were decreased when A549 COX-2 sense cell was transduced with Ad-UG (50 moi). (B) Transfection with COX-2 siRNA (50 nM) to A549 cell inhibited not IDO but COX-2. (C) A549 COX-2 sense cell transfected with siRNA (50 nM) had same result B. Uteroglobin suppressed IDO protein level both B and C. It need further study about IDO enzyme activity test with uteroglobin.
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