Differential induction of cytokine genes and activation of mitogen-activated protein kinase family by soluble CD40 ligand and TNF in a human follicular dendritic cell line.
Follicular dendritic cells (FDC)3 play crucial roles in germinal center (GC) formation and differentiation of GC B cells. Many aspects of FDC function are influenced by contact with B or T cells, and by cytokines produced in the GC, which involve stimulation of CD40 and TNF-alpha receptors on FDC. In this study, using an established FDC line, HK cells, we compared the effects of CD40 and TNF receptor triggering on cytokine induction and activation of mitogen-activated protein kinase family. We show that HK cells spontaneously produced IL-6, M-CSF, and G-CSF mRNA. Both the soluble form of CD40 ligand (sCD40L) and TNF increased the level of M-CSF and G-CSF mRNA. While TNF strongly induced IL-6 mRNA, its expression was not affected by sCD40L treatment, differing from the strong IL-6 induction in other cell types upon CD40 stimulation. In addition, sCD40L treatment resulted in activation of extracellular signal-related kinase 1 and 2 (ERK1/2) and p38 without significant increase in c-Jun N-terminal kinase (JNK) activity. Lack of JNK activation differs in that most B cells respond to CD40 stimulation by inducing JNK activity strongly, suggesting distinct characteristics of CD40 signaling in FDC. Compared with the effects of sCD40L, TNF was capable of inducing JNK activity in addition to the activation of ERK1/2 and p38. Furthermore, the proximal signaling elements activated by TNF differed from those activated by sCD40L, in that TNF did not require PMA-sensitive protein kinase C isoforms in the activation of ERK and p38, whereas sCD40L did. However, signals activated by these stimuli converged on cytokine gene expression in a synergistic manner, which may have implication in augmenting FDC function during GC reaction.
Department of Biology, College of Science, Yonsei University, Seoul, Korea.
S M
SM
Park
H S
HS
Kim
J
J
Choe
T H
TH
Lee
D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004789:Enzyme Activation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D019013:CD40 Antigens; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate