Multiple signaling pathways are involved in the interleukine-4 regulated expression of DC-SIGN in THP-1 cell line.
Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) is an important pattern recognition receptor on dendritic cells (DCs), and its expression shows significant cytological and histological specificity, being interleukine-4 (IL-4) dependent. The signaling pathways through which IL-4 regulates expression of DC-SIGN are still unclear. We used phorbol 12-myristate 13-acetate- (PMA-) differentiated THP-1 cells as the in vitro model of monocyte/macrophage cells to study the signaling pathways involved in IL-4-regulated expression of DC-SIGN. We found that a high expression of DC-SIGN could be induced by IL-4 at the levels of mRNA and cell surface protein. Upregulated expression of DC-SIGN was almost completely blocked by the specific inhibitor of ERK pathway, and partly reduced by the specific inhibitors of JAK-STAT and NF-κB pathways. The activation of the three signaling pathways was directly confirmed by testing the phosphorylation of protein kinase within the cytoplasm and nucleus over time. The analysis of cis-acting elements of DC-SIGN promoter showed that the activity of DC-SIGN promoter without Ets-1 transcription factors binding site almost completely disappeared. Our results demonstrated that multiple signaling pathways are involved in IL-4 induced high expression of DC-SIGN on THP-1 cells, in which ERK pathway is the main signaling pathway and mediated by the Ets-1 transcription factors binding site.
State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Changzhong
C
Jin
Lijuan
L
Wu
Jie
J
Li
Meixin
M
Fang
Linfang
L
Cheng
Nanping
N
Wu
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015847:Interleukin-4; D053612:Janus Kinases; D037181:Lectins, C-Type; D016328:NF-kappa B; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D050791:STAT Transcription Factors; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C494041:ETS1 protein, human