title: [Expression of CC-chemokine ligand 18 (CCL18) in the serum and pleural effusion of non-small-cell lung cancer patients and its regulatory effect on the differentiation of monocyte-derived dendritic cells].
abstract: OBJECTIVE
  To compare the CC-chemokine ligand 18 (CCL18) expression in the serum and malignant pleural effusion (MPE) of NSCLC patients and explore its regulatory effect on differentiation of monocyte-derived dendritic cells (Mo-DC).
  
  
  METHODS
  CCL18 levels in the serum and MPE from 62 NSCLC patients were quantitated by immunoassay. CCL18 in sera from 26 healthy individuals, 28 exudative pleural effusions from inflammatory pulmonary diseases and 17 transudative pleural effusions from non-inflammatory diseases were used as control. Mo-DC was generated by culturing NSCLC-derived monocytes with GM-CSF and IL-4 in the presence or absence of CCL18. The mean fluorescent intensity (MFI) of CD14, CD80, CD83, CD86 and HLA-DR were analyzed by flow cytometry (FCM). Mo-DC was then co-cultured with purified T cells and the percence of CD25(+)FoxP3(+) cells was assayed by FCM.
  
  
  RESULTS
  CCL18 levels in the sera of NSCLC patients and healthy individuals were (132.70 ± 15.52) ng/ml and (18.44 ± 0.99) ng/ml, respectively (P < 0.001). The levels of CCL18 in MPE, exudative PE and transudative PE were (155.6 ± 13.58) ng/ml, (190.4 ± 22.33) ng/ml and (20.89 ± 3.03) ng/ml, respectively. CCL18 in the MPE was significantly higher than that in transudates (P < 0.001), however, no significant difference was observed between CCL18 expression in exudative PE and MPE (P = 0.172). Of note, a moderate positive correlation (r = 0.421, P < 0.01) was observed between CCL18 levels in the paired MPE and serum of NSCLC. In the healthy control group, Mo-DC cultured in the presence of CCL18 showed 31.4 ± 15.8 (MFI) of CD14 expression, which was significantly higher than that in Mo-DC cultured in the absence of CCL18 (18.5 ± 8.9, P < 0.05). In contrast, the expressions of MFI of CD80, CD83, CD86 and HLA-DR were significantly decreased upon CCL18 induction (P < 0.05). In the NSCLC group, GM-CSF+IL-4+CCL18 induced a MFI of 45.2 ± 13.8 of CD14 expression in Mo-DC, which was also significantly higher than that of GM-CSF+ IL-4 induction (22.6 ± 10.5, P < 0.01). Similarly, the expressions of MFI of CD80, CD83, CD86 and HLA-DR were significantly decreased in the presence of CCL18 (P < 0.05). Furthermore, the MFI of CD14, CD83, CD86 and HLA-DR had significant differences between GM-CSF/IL-4/CCL18-induced Mo-DC derived from NSCLC patients and healthy control (P < 0.05). Finally, CD4(+) T cells co-cultured with NSCLC-derived, GM-CSF/IL-4/CCL18-treated Mo-DC had significantly higher percent of CD25(+)FoxP3(+) cells compared with that of CD4(+) T cells stimulated with Mo-DC induced by GM-CSF/IL-4(P < 0.01).
  
  
  CONCLUSIONS
  CCL18 is present at a high level in MPE and serum of NSCLC patients complicated with pleural effusion and a moderate positive correlation exists between CCL18 levels in the two fluids. CCL18 inhibits maturation of Mo-DC, which consequently stimulates T cells to differentiate into CD25(+)FoxP3(+) regulatory T cells.
authors.affiliation: Clinical Laboratory, the Second Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Fang
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: Email: shiheguan@126.com.
authors.forename: Shihe
authors.initials: S
authors.lastname: Guan
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002454:Cell Differentiation; D018925:Chemokines; D019742:Chemokines, CC / Q000378:metabolism*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000378:metabolism; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008024:Ligands; D008175:Lung Neoplasms; D009000:Monocytes / Q000502:physiology*; D010996:Pleural Effusion; D050378:T-Lymphocytes, Regulatory
chemical_list: C111792:CCL18 protein, human; D018925:Chemokines; D019742:Chemokines, CC; D008024:Ligands; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor