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The immune modulation of Clara cell-10 in human peripheral monocytes and dendritic cells

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Authors
Yoon, Jung Min; Lee, Kyu-Hwa; Lee, Sang Min; Lim, Jae-Jun; Yoo, Chul-Gyu; Han, Sung Koo; Kim, Young Whan; Shim, Young-Soo; Lee, Choon-Taek; Yang, Seok-Chul
Issue Date
2010-09
Publisher
SPANDIDOS PUBL LTD
Citation
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE; Vol.26 3; 415-423
Keywords
Clara cell secretory proteincyclooxygenase-2immune modulation
Abstract
Although Clara cell secretory protein (CC-10, CC-16 or uteroglobin, secretoglobin 1A1) has been ascribed anti-inflammatory, immunomodulatory and anti-cancer activity roles in lung diseases including lung cancer, its precise function remains unclear. The objective of the present study was to evaluate the role of CC-10 in the immunomodulation of human monocytes and dendritic cells (DCs). The human lung adenocarcinoma cell line A549, was used to examine PGE2 production after cyclooxygenase (COX) inhibition and adenovirus encoding human CC-10 cDNA (Ad-CC-10) transfection. Type I and II cytokines were measured from peripheral blood mononuclear cells (PBMCs) and DCs which were cultured with tumor supernatant (TSN) or Ad-CC-10 transfected TSN. When PBMCs were cultured with supernatant A549 (tumor supernatant, TSN), the levels of T-cell helper type 1 (Th1) and 2 (Th2) cytokines increased. However. CC-10 inhibited the induction of Th2 cytokines of PBMCs stimulated with TSN. In DCs, TSN inhibited Th1 type cytokines but induced Th2 type. In contrast, TSN treated with either CC-10 or NS398 (COX-2 inhibitor) stimulated Th1 type and inhibited Th2 type without any phenotypic changes. The supernatants generated in the presence of NS-398 or CC-10 prevented tumor-induced inhibition of allogeneic T-cell stimulation. While the level of interleukin (IL)-10 secretion from DC-Ad-CC-10 was decreased, the level of IL-12 secretion was increased by CC-10. Collectively our data suggest that a supernatant of NSCLC causes an imbalance in the immune response of PBMCs and DCs, which is reversed by CC-10. This suggests that CC-10 is a candidate for the development of a new immunotherapy for lung cancer.
ISSN
1107-3756
Language
English
URI
https://hdl.handle.net/10371/77441
DOI
https://doi.org/10.3892/ijmm_00000481
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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