TNF Production in Activated RBL-2H3 Cells Requires Munc13-4
Document Type
Article
Publication Date
1-2-2020
School
Biological, Environmental, and Earth Sciences
Abstract
Mast cell activation triggers intricate signaling pathways that promote the expression and/or release of a wide range of mediators including tumor necrosis factor (TNF; also known as TNFα). In this study, we investigated the connection between TNF secretion and TNF production, exploiting RBL-2H3 cells (a tumor analog of mucosal mast cells) that are depleted of Munc13-4, a crucial component of the mast cell exocytic machinery. We showed that antigen/IgE elicited robust TNF production in RBL-2H3 cells, but not in Munc13-4 knockout cells. The production defect was corrected when Munc13-4 was reintroduced into the knockout cell line, suggesting that the phenotype was not caused by any secondary effect derived from the knockout approach. Furthermore, pre-incubation of RBL-2H3 cells with R-7050, an antagonist of TNF receptor-dependent signaling, was shown to block TNF production without inhibiting TNF release. These observations provide fresh evidence for a robust feed-back loop to boost TNF production in activated mast cells.
Publication Title
Inflammation
Volume
43
First Page
744
Last Page
751
Recommended Citation
Ayo, T. E.,
Adhikari, P.,
Sugita, S.,
Xu, H.
(2020). TNF Production in Activated RBL-2H3 Cells Requires Munc13-4. Inflammation, 43, 744-751.
Available at: https://aquila.usm.edu/fac_pubs/17375