Multifunctional cytokine expression by human mast cells: Regulation by T cell membrane contact and glucocorticoids

G. Krishnaswamy, T. Lakshman, A. R. Miller, S. Srikanth, K. Hall, S. K. Huang, J. Suttles, J. K. Smith, R. Stout

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Abstract

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.

Original languageEnglish
Pages (from-to)167-176
Number of pages10
JournalJournal of Interferon and Cytokine Research
Volume17
Issue number3
DOIs
Publication statusPublished - Jan 1 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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