The immune modulation of Clara cell-10 in human peripheral monocytes and dendritic cells.
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.
Yoon
Jung Min
JM
Lung Institute of Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Lee
Kyu-Hwa
KH
Lee
Sang Min
SM
Lim
Jae-Jun
JJ
Yang
Seok-Chul
SC
Yoo
Chul-Gyu
CG
Lee
Choon-Taek
CT
Han
Sung Koo
SK
Shim
Young-Soo
YS
Kim
Young Whan
YW
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D017077:Culture Media, Conditioned / Q000737:chemistry; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology / Q000503:physiopathology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010641:Phenotype; D014598:Uteroglobin / Q000235:genetics / Q000276:immunology*
D017077:Culture Media, Conditioned; D016207:Cytokines; C556389:SCGB1A1 protein, human; D014598:Uteroglobin