Recombinant TAT-CD137 Ligand Cytoplasmic Domain Fusion Protein Induces the Production of IL-6 and TNF-${\alpha}$ in Peritoneal Macrophages

• Published in: Immune network Vol. 11; no. 4; pp. 216 - 222
• Main Authors: Kim, Jung-D, Lee, Eun-A, Quang, Nguyen N, Cho, Hong-R, Kwon, Byung-Suk
• Format: Journal Article
• Language: Korean
• Published: 2011
• Subjects: CD137 ligand; TAT; Peritoneal macrophages; CD137; Reverse signaling
• ISSN: 1598-2629; 2092-6685

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-${\alpha}$ 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-${\kappa}B$ ($IkB{\alpha}$). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-${\alpha}$, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-${\alpha}$ production. Conclusion: Our results suggest that TATCD137Lct is an effective activator for the CD137L reverse signaling pathway.