Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy.
Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.
Ishii
Kazuo
K
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
Kurita-Taniguchi
Mitsue
M
Aoki
Mikio
M
Kimura
Toru
T
Kashiwazaki
Yasuo
Y
Matsumoto
Misako
M
Seya
Tsukasa
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002454:Cell Differentiation; D017358:Cell Wall Skeleton / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D007372:Interferons / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009163:Mycobacterium bovis / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D010457:Peptidoglycan / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D017358:Cell Wall Skeleton; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D012333:RNA, Messenger; D007372:Interferons