Tuberc Respir Dis.  2009 Apr;66(4):274-279.

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

• Park GM
• Lee SM
• Yim JJ
• Yang SC
• Yoo CG
• Lee CT
• Han SK
• Shim YS
• Kim YW

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.

Keyword

Uteroglobin; Cyclooxygenase 2; Indoleamine 2; 3-dioxygenase; Interferon-gamma; Immune tolerance

MeSH Terms

Carcinoma, Non-Small-Cell Lung
Cell Line
Constitution and Bylaws
Cyclooxygenase 2
Immune Tolerance
Indoleamine-Pyrrole 2,3,-Dioxygenase
Interferon-gamma
Kynurenine
Lung
Prostaglandin-Endoperoxide Synthases
RNA, Small Interfering
Tryptophan
Uteroglobin
Cyclooxygenase 2
Indoleamine-Pyrrole 2,3,-Dioxygenase
Interferon-gamma
Kynurenine
Prostaglandin-Endoperoxide Synthases
RNA, Small Interfering
Tryptophan
Uteroglobin

Figure

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  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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