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-1, we show expression of cytokine transcripts as early as 2 h after activation with ionomycin and phorbol myristate acetate (PMA). Resting HMC-1 cells expressed transcripts for interleukin-1 receptor antagonist (IL-1RA), 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. HMC-1 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-1 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
G
Department of Medicine, East Tennessee State University, Johnson City 37614-0622, USA.
Lakshman
T
T
Miller
A R
AR
Srikanth
S
S
Hall
K
K
Huang
S K
SK
Suttles
J
J
Smith
J K
JK
Stout
R
R
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019013:CD40 Antigens / Q000097:blood; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8 / Q000235:genetics; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D016207:Cytokines; D005938:Glucocorticoids; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D003907:Dexamethasone