Theoharides, Mast Cells, Autism, Inflammation

Dr. Theoharides at Tufts University

The research focuses on the secretory mechanism and pathophysiological actions of mast cells. Diseases investigated include: atopic dermatitis, arthritis, autism, coronary artery inflammation, interstitial cystitis, migraines and multiple sclerosis. These diseases worsen by stress and we have identified that mast cells both contain and respond to stress hormones. The techniques used include molecular biology, cell biology, and various microscopic techniques, as well as animal models for the target diseases in which mast cells are involved.

Lecture Slides

Treating Autism 7th Biomedical Conference - UK
June 18-19, 2011
Aberrant inflammatory response in autism—Mast cell activation and the latest research in novel biomarkers and treatment directions
Download Lecture Slides: [PowerPoint] or [PDF]

Research Categories

Autism

• Autism, Seizures, JNI 2012
• Autism, Allergies JADD
• Inflammatory Conditions (Quicktime video)
• The Immune System & Autism (Quicktime/Flash Video)
• Novel therapeutic targets for autism
• Mast cells as targets of corticotropin releasing factor and related peptides
• Critical role of mast cells in inflammatory diseases and
the effect of acute stress
• Autism: an emerging ‘neuroimmune disorder’ in search of therapy
• Autism Spectrum Disorders and Mastocytosis
• Mercury induces inflammatory mediator release from human mast cells
• Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children
• Neurotensin is increased in serum of young children with autistic disorder

Brain Health

• Stress Blood Brain Barrier
• Brain Inflammation
• Non-steroidal Drugs Inhibit SSRI Antidepressant Action
• Mast Cells - The Immune Gate to the Brain

Fibromyalgia / Chronic Fatigue

• Fibromyalgia - New Concepts Of Pathogenesis And Treatment

Interstitial Cystitis

• When to Suspect Interstitial Cystitis
• Inflammatory Conditions (Quicktime video)
• CystoProtek® (video)
• Increased Numbers of Activated Mast Cells in Endometriosis Lesions Positive for Corticotropin-Releasing Hormone and Urocortin
• Treatment of refractory interstitial cystitis/
painful bladder syndrome with CystoProtek
– an oral multi-agent natural supplement
• A Pilot Open Label Study Of Cystoprotek In Interstitial Cystitis
• New agents for the medical treatment of interstitial cystitis
• Interstitial cystitis: bladder pain and beyond
• Acute Stress and Intravesical Corticotropin-Releasing Hormone Induces Mast Cell Dependent Vascular Endothelial Growth Factor Release From Mouse Bladder Explants
• Intravesical Nanocrystalline Silver Decreases Experimental Bladder Inflammation
• Intravesical Suplatast Tosilate (IPD-1151T) Inhibits Experimental Bladder Inflammation
• The Mast Cell in Interstitial Cystitis: Role in
Pathophysiology and Pathogenesis
• Immunomodulators For Treatment Of Interstitial Cystitis

Arthritis

• Mast cells and mast cell mediators as targets of dietary supplements
• Chondroitin sulphate inhibits connective tissue mast cells
• Mast Cell Deficient W/Wv Mice Lack Stress-Induced Increase In Serum Il-6 Levels, As Well As In Peripheral Crh And Vascular Permeability, A Model Of Rheumatoid Arthritis
• Dietary Supplements For Arthritis And Other Inflammatory Conditions: Key Role Of Mast Cells And Benefit Of Combining Anti-Inflammatory And Proteoglycan Products

Mastocytosis

• Quercetin Better Than Cromolyn
• CRH, BBB-Bioscience Differential release of mast cell mediators and the pathogenesis of inflammation
• Neuroimmunoendocrine circuitry of the ‘brain-skin connection’
• Secondary Anetoderma Associated with Mastocytosis
• Acute Stress-Induced Seizures and Loss of Consciousnenn in a Ten-Year-Old Boy With Cutaneous Mastocytosis
• Urticaria pigmentosa associated with acute stress and lesional skin mast-cell expression of CRF-R1

Skin Diseases

• Regulation of corticotropin-releasing hormone receptor-2 expression in human cord blood-derived cultured mast cells
• Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process
• Human Mast Cells Express Corticotropin-Releasing Hormone (CRH) Receptors and CRH Leads to Selective Secretion of Vascular Endothelial Growth Factor
• Corticotropin-Releasing Hormone Induces Vascular Endothelial Growth Factor Release from Human Mast Cells via the cAMP/Protein Kinase A/p38 Mitogen-Activated Protein Kinase Pathway
• Acute Stress Results in Skin Corticotropin- Releasing Hormone Secretion, Mast Cell Activation and Vascular Permeability, an Effect Mimicked by Intradermal Corticotropin- Releasing Hormone and Inhibited
by Histamine-1 Receptor Antagonists
• Skin Corticotropin-Releasing Hormone Receptor Expression in Psoriasis
• IL-33 augments substance P–induced VEGF secretion
from human mast cells and is increased in psoriatic skin
• Corticotropin-Releasing Hormone Receptor-1 and Histidine Decarboxylase Expression in Chronic Urticaria
• A Quercetin Containing Supplement Reduces Niacin-Induced Flush In Humans
• Rupatadine Inhibits Proinflammatory Mediator Secretion from Human Mast Cells Triggered by Different Stimuli
• Neuroimmunoendocrine circuitry of the 'brain-skin connection'
• Potent Mast Cell Degranulation and Vascular Permeability Triggered by Urocortin Through Activation of Corticotropin- Releasing Hormone Receptors
• Urticaria pigmentosa associated with acute stress and lesional skin mast-cell expression of CRF-R1

Multiple Sclerosis

• IJIP MS Hydroxyzine
• Luteolin, MS, TCT, J Neuroinflam 11-09
• Luteolin, T cells, mast cells BJP 2008
• Monkey EAE
• Mast Cells The Immune Gate to the Brain LIfe Sciences 1990
• MBB, estradiol activate brain mast cells, demyelination, Neuroscience

Cancer

• Mast cells and pancreatic cancer
Mast cells: the JEKYLL and HYDE of tumor growth
• Brain metastases of mouse mammary adenocarcinoma is increased by acute stress
• Impact of stress and mast cells on brain metastases
• Mast Cells and Tumor Microenvironment

Brain Inflammation

• Histochemical and Ultrastructural Characteristics of Rat Barin Perivascular Mast Cell Stimulated With Compound 48/80 and Carabachol
• Definitive Characterization of Rat Hypothalamic Mast Cells
• The role of mast cells in migraine pathophysiology
• Corticotropin-releasing hormone and the blood-brain-barrier
• Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress
• Definitive Characterization of Rat Hypothalamic Mast Cells
• Nasal provocation of patients with allergic rhinitis and the hypothalamic-pituitary-adrenal axis
• Critical role of mast cells in inflammatory diseases and the effect of acute stress
• Acute stress increases permeability of the blood–brain-barrier through activation of brain mast cells
• Non-invasive assessment of blood–brain barrier (BBB) permeability using a gamma camera to detect 99technetium-gluceptate extravasation in rat brain
• Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice

Cardiovascular Diseases

• The Role of Mast Cells in Acute Coronary Syndromes
• Sites of Interleukin-6 Release in Patients With Acute Coronary Syndromes and in Patients With Congestive Heart Failure
• Stress-induced interleukin-6 release in mice is mast cell-dependent and more pronounced in Apolipoprotein E knockout mice
• IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells
• Kounis Syndrome (Allergic Angina and Allergic Myocardial Infarction)
• Coronary Stents, Hypersensitivity Reactions, and the Kounis Syndrome
• The flavonoid luteolin inhibits niacin-induced flush
• Allergic Inflammation and Adipocytokines
• The flavonoid luteolin inhibits niacin-induced flush
• Niacin-induced "Flush" Involves Release of Prostaglandin D2 from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model
• Mast Cell Deficient W/W Mice Have Lower Serum IL-6 and Less Cardiac Tissue Necrosis Than Their Normal Littermates Following Myocardial Ischemia-Reperfusion
• Mast cell tryptase: a new biomarker in patients with stable coronary artery disease
• Mast cell tryptase: a new biomarker in patients with stable coronary artery disease
• Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-kB activation

Flavonoids

• Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells
• Flavones inhibit proliferation and increase mediator content in human leukemic mast cells (HMC-1)
• The Effects of Plant Flavonoids on Mammalian Cells:
Implications for Inflammation, Heart Disease,
and Cancer
• The Isoflavone Genistein Inhibits Proliferation and Increases Histamine Content in Human Leukemic Mast Cells
• The flavonoid luteolin inhibits niacin-induced flush
• Luteolin as a therapeutic option for multiple sclerosis
• Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell-dependent stimulation of Jurkat T cells
• The flavonoid luteolin inhibits niacin-induced flush

Mast Cells and Inflammation

• Differential release of mast cell mediators and the pathogenesis of inflammation
• Critical role of mast cells in inflammatory diseases and the effect of acute stress
• The Critical Role of Mast Cells in Allergy and Inflammation

Migraines

• The role of mast cells in migraine pathophysiology
• Corticotropin-releasing hormone and the blood-brain-barrier
• Morphological and functional demonstration of rat dura mater mast cell–neuron interactions in vitro and in vivo
• Nasal provocation of patients with allergic rhinitis and the hypothalamic-pituitary-adrenal axis
• Corticotropin-Releasing Hormone and Its Structurally Related Urocortin Are Synthesized and Secreted by Human Mast Cells
• Mast Cells: The Immune Gate To The Brain
• Migraine Headaches: The Immunologist's View
• Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice
• Stress-Induced Intracranial Mast Cell Degranulation: A Corticotropin-Releasing Hormone-Mediated Effect
• Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice
• Mast cells as targets of corticotropin- releasing factor and related peptides