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

Park, Gun Min; Lee, Sang Min; Yim, Jae Joon; Yang, Seok Chul; Yoo, Chul Gyu; Lee, Choon Taek; Han, Sung Koo; Shim, Young Soo; Kim, Young Whan

doi:2009.66.4.274

Tuberc Respir Dis > Volume 66(4); 2009 > Article

Original Article

Tuberculosis and Respiratory Diseases 2009;66(4):274-279.
DOI: https://doi.org/10.4046/trd.2009.66.4.274 Published online April 1, 2009.

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

Gun Min Park, Sang Min Lee, Jae Joon Yim, Seok Chul Yang, Chul Gyu Yoo, Choon Taek Lee, Sung Koo Han, Young Soo Shim, Young Whan Kim

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. ywkim@snu.ac.kr
³Respiratory Center, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

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-gamma) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-gamma 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.

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