UCP2 – Mast Cells and Autism

Mast Cell Secretion and the Mitochondrial Uncoupling Protein UCP2


The Theoharis Theoharides Lab – Tufts University Sackler School of Graduate Biomedical Sciences


Mast Cells and Disease Processes

Mast cells are known for their involvement in allergic reactions, but we were the first to show that they are also necessary to inititate inflammation, thus participating in inflammatory diseases that worsen by stress, such as autism, cancer,  chronic fatigue syndrome, interstitial cystitis, migraine headaches, psoriasis and  multiple sclerosis.  We have developed in vivo and in vitro models for these diseases and we are studying neurohormonal activation of mast cells.  The only plausible way to explain how mast cells can participate in so many diverse processes is their ability to secrete distinct chemicals relative for different pathophysiological settings.

Molecular Events Involved in Mast Cell Stimulus-Secretion Coupling

Mast cells are typically activated by immunoglobulin E and antigen, a process that leads to an explosive release of over 20 biologically active molecules (some of which are presorted in some 500 secretory grqnules, wile others are synthesized during activation) through a process called degranulation or exocytosis.  However, we were the first to show that mast cells can also respond to non-allergic triggers and release mediators selectively, without degranulation. We specifically reported that the inflammatory cytokine IL-1 can induce selective release of the also inflammatory cytokine IL-6, that the stress hormone corticotropin-releasing hormone (CRH) can induce selective release of vascular endothelial growth factor (VEGF), and IL-33 augments substance P-induced VEGF release.  We are currently studying the regulation of CRH receptor expression and function on human cultured mast cells and the effects of their respective activation on allergic stimulation.

Mast Cell Secretion and the Mitochondrial Uncoupling Protein UCP2

We showed for the first time that there is an inverse relationship between UCP2 expression and mast cell secretion.  We also showed for the firtst time that mast cell degranulation, but not selective release of tumor necrosis factor (TNF), is associated with mitochondrial fission and relocation from perinuclear localization to cell-widespread distribution.


Further Reading

Perinatal stress and brain inflammation.


Allergies and Cancer and Antibodies


Luteolin Autism – Treatment


Mast Cells and Autism – Treatment possibilities


Allergy , Mast Cells and GI issues


Allergy : New Thinking





This entry was posted in Allergy, Asthma, Autism, co-morbid, Environment, Immune System, Inflammation, Neurology, Physiology. Bookmark the permalink.

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