Induction of suppressive phenotype in monocyte-derived dendritic cells by leukemic cell products and IL-1β.
Professional antigen-presenting cells, dendritic cells (DCs) play an important role in controlling tumors. It is known that solid tumor cell products inhibit DC differentiation. Recently a similar effect produced by leukemic cell products has been demonstrated. In this case, leukemic cell products induced the secretion of IL-1β by monocytes undergoing differentiation. The aim of the present work was to characterize and to compare the development of monocyte-derived DCs under the influence of leukemic cell products (K562 supernatant) or exogenous IL-1β. It became clear that leukemic cell products and IL-1β differentially modulate some of the parameters studied on monocytes stimulated to differentiate into DCs. In the presence of K562 supernatant, the expression of the macrophage markers CD16 and CD68 were higher than in immature DCs control. Contrasting with IL-1β, leukemic cell products possibly favor the development of cells with macrophage markers. In addition, CD80 and CD83 expressions were also higher in the presence of tumor supernatant whereas HLA-DR was lower. In the presence of IL-1β, only CD80 was increased. Furthermore, it was observed that when monocytes were induced to differentiate into DCs in the presence of tumor supernatant and then activated, they expressed less CD80 and CD83 than activated DCs control. A reduced expression of CD83 following activation was also seen in cells differentiated with IL-1β. TGF-β and VEGF were found in the tumor supernatants. Moreover, the exposure to tumor supernatant or IL-1β stimulated IL-10 production while decreased IL-12 production by activated DCs. Finally, these results suggest that the addition of products released by leukemic cells or, more discreetly, the addition of IL-1β affects DC differentiation, inducing a suppressive phenotype.
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Juliana Maria
JM
Motta
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Aline
A
Sperandio
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Morgana Teixeira Lima
MT
Castelo-Branco
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: vivian@bioqmed.ufrj.br.
Vivian Mary
VM
Rumjanek
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D020014:K562 Cells; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype; D061251:Primary Cell Culture; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097802:CD83 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018122:B7-1 Antigen; D017077:Culture Media, Conditioned; D058851:GPI-Linked Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D016753:Interleukin-10; D018664:Interleukin-12; D053583:Interleukin-1beta; D015847:Interleukin-4; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C428200:FCGR3B protein, human; C508609:IL10 protein, human; C508598:IL4 protein, human
Dendritic cell activation; Dendritic cell differentiation; IL-1β; Leukemic cell products; Suppressive phenotype