Tuberc Respir Dis.  2004 Oct;57(4):336-344.

The Role of Uteroglobin in the Immunomodulation of Nonsmall Cell Lung Cancer Cells

• Yoon JM
• Lim JJ
• Yoo CG
• Lee CT
• Han SK
• Shim YS
• Kim YW

Abstract

BACKGROUND: Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer.
METHODS
The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin E2 (PGE2) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA.
RESULTS
UG suppressed PGE2, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-gamma (IFN-gamma) and Tumor necrosis factor-alpha (TNF-alpha) and Th2 type cytokines such as IL-10 and Tumor growth factor-beta (TGF-beta) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG.
CONCLUSION
UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

Keyword

Uteroglobin; Lung cancer; PBMC

MeSH Terms

Carcinoma, Non-Small-Cell Lung*
Cell Line
Cyclooxygenase 2
Cytokines
Dinoprostone
Enzyme-Linked Immunosorbent Assay
Ficoll
Immunoenzyme Techniques
Immunomodulation*
Immunotherapy
Intercellular Signaling Peptides and Proteins
Interferon-gamma
Interleukin-10
Interleukin-2
Lung Neoplasms
Tumor Necrosis Factor-alpha
Uteroglobin*
Cyclooxygenase 2
Cytokines
Dinoprostone
Ficoll
Intercellular Signaling Peptides and Proteins
Interferon-gamma
Interleukin-10
Interleukin-2
Tumor Necrosis Factor-alpha
Uteroglobin