Inhibition of mouse mast cell proliferation and proinflammatory mediator release by benzodiazepines

• Published in: Immunopharmacology 1999-06, Vol.43 (1), p.75-86
• Main Authors: Bidri, Mohamed, Royer, Bernard, Averlant, Geneviève, Bismuth, Georges, Guillosson, Jean-Jacques, Arock, Michel
• Format: Article
• Language: English
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; beta-N-Acetylhexosaminidases - secretion; Biological and medical sciences; Cell Division - drug effects; Diazepam; Diazepam - pharmacology; Histamine and antagonists. Allergy; Hypnotics. Sedatives; In Vitro Techniques; Inflammation Mediators - metabolism; Male; Mast cell; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Midazolam; Midazolam - pharmacology; Neuropharmacology; Nitrites; Nitrites - metabolism; Pharmacology. Drug treatments; Phenotype; Proliferation; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; TNF-alpha; Tumor Necrosis Factor-alpha - secretion
• ISSN: 0162-3109
• DOI: 10.1016/S0162-3109(99)00046-6

Mast cell (MC) activation may occur in vitro and in vivo following stimulation with various immunologic or nonimmunologic agents. Such activation leads to the release of several biological mediators, including vasoactive amines, nitric oxide and cytokines, which account for the adverse effects observed during allergic reactions. While high affinity binding sites for benzodiazepines (BZDs) have been reported on MC, the effects of the ligation of these receptors on the proliferation of, and the mediator release from, these cells are poorly documented. In the present work, we have examined the effects of midazolam and of diazepam on the proliferation of mucosal (MMC)-like and of serosal (CTMC)-like mouse MC. In addition, we have studied the effects of these BZDs on β-hexosaminidase, TNF-α and nitrite release induced from mouse mast cells through IgE receptor activation. We demonstrated that each of the two BZDs studied inhibited the proliferation of MMC- and CTMC-like elements in a dose-dependent fashion (10 to 100 μM). Furthermore, the BZDs inhibited the IgE-mediated release of β-hexosaminidase, TNF-α and nitrites from MMC- or CTMC-like cells. Altogether, these data provide new insights into the pharmacological regulation of MC activation and may lead to the discovery of new and potent antiallergic compounds.