Multifunctional Cytokine Expression by Human Mast Cells: Regulation by T Cell Membrane Contact and Glucocorticoids
Human mast cells readily release a variety of mediators, including cytokines, in response to IgE receptor crosslinking, but the mechanisms governing the expression of cytokines are still unclear. Using a human mast cell line, HMC-I, we show expression of cytokine transcripts as early as 2 h after activation with ionomycin and phorbol myristate acetate (PMA). Resting HMC-I cells expressed transcripts for interleukin-1 receptor antagonist (IL- IRA), IL-2, IL-4, IL-5, GM-CSF, and weakly for IL-8, and stimulation with ionomycin and PMA induced additional transcripts for IL-6 and IL-13 and upregulated expression of IL-8 transcripts. HMC1 cells secreted IL-4, IL-8, and GM-CSF protein after activation and dexamethasone significantly inhibited the production of these cytokines. Of significance is the finding that the addition of membranes purified from activated T cells to mast cell cultures induced transcripts selectively for IL-8 and none for other proinflammatory cytokines. Flow cytometry revealed that resting HMC-1 cells express CD40, a molecule involved in contact-dependent signaling of monocytes and B cells by T cells. However, activation of HMC-I by anti-CD40 antibody did not induce IL-8 gene expression or protein production. This study demonstrates that human mast cells are capable of expressing multiple cytokines that can be inhibited by glucocorticoids. It also raises the possibility that T cells may activate mast cell cytokine synthesis by novel contact-dependent mechanisms. This phenomenon of T cell regulation of mast cell function requires further study.
Krishnaswamy, G.; Lakshman, T.; Miller, A. R.; Srikanth, S.; Hall, K.; Huang, S. K.; Suttles, J.; Smith, J. K.; and Stout, R.. 1997. Multifunctional Cytokine Expression by Human Mast Cells: Regulation by T Cell Membrane Contact and Glucocorticoids. Journal of Interferon and Cytokine Research. Vol.17(3). 167-176. https://doi.org/10.1089/jir.1997.17.167 PMID: 9085942 ISSN: 1079-9907