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KMID : 0923620110110040216
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Immune Network
2011 Volume.11 No. 4 p.216 ~ p.222
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Recombinant TAT-CD137 Ligand Cytoplasmic Domain Fusion Protein Induces the Production of IL-6 and TNF-? in Peritoneal Macrophages
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Kim Jung-D.
Lee Eun-A.
Quang Nguyen-N.
Kwon Byung-suk
Cho Hong-R.
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Abstract
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Background: The ligand for CD137 (CD137L; also called 4-1BBL) is mainly expressed on activated APCs such as dendritic cells, B cells and macrophages. Even though CD137L functions as a trigger of the CD137 signaling pathway for T cell activation and expansion, engagement of CD137L can deliver a signal leading to the production of proinflammatory cytokines in macrophages.
Methods:We generated cell-permeable TAT-CD137L cytoplasmic domain fusion protein (TAT-CD137Lct) and examined its ability to initiate the CD137L reverse signaling pathway.
Results: Treatment of TAT-CD137Lct induced the production of high levels of IL-6 and TNF-? mRNAs and proteins in peritoneal macrophages. TAT-CD137Lct increased phosphorylation of Erk, p38 MAPK and Jnk, and activated transcription factors C/EBP and CREB. However, TAT-CD137Lct did not visibly affect the degradation of the inhibitor of NF-kB (IkB?). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-?, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-? production.
Conclusion: Our results suggest that TAT- CD137Lct is an effective activator for the CD137L reverse signaling pathway.
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KEYWORD
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CD137 ligand, CD137, Reverse signaling, TAT, Peritoneal macrophag
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