Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content

Michael Tagen, Alvaro Elorza, Duraisamy Kempuraj, William Boucher, Christopher L. Kepley, Orian S. Shirihai, Theoharis C. Theoharides

Resultado de la investigación: Article

38 Citas (Scopus)

Resumen

Mast cells are immune effector cells that are involved in allergies and inflammation through the release of mediators such as histamine, PGs, and cytokines. Uncoupling protein 2 (UCP2) is a mitochondrial protein that inhibits insulin secretion from β cells, possibly through down-regulation of reactive oxygen species production. We hypothesized that UCP2 could also regulate mast cell activation. In this study, we show that mouse bone marrow mast cells (BMMCs) and human leukemic LAD2 mast cells express UCP2. BMMCs from Ucp2-/- mice exhibited greater histamine release, whereas overexpression of UCP2 in LAD2 cells reduced histamine release after both allergic and nonallergic triggers. Ucp2-/- BMMCs also had elevated histamine content and histidine decarboxylase expression. Histamine content was reduced by overexpression of UCP2 or treatment with the mitochondrial-targeted superoxide dismutase-mimetic (TBAP) tetrakis(4-benzoic acid) porphyrin manganese(III). Furthermore, Ucp2-/- BMMCs also had greater production of both IL-6 and PGD2 as well as ERK phosphorylation, which is known to regulate PG synthesis. Intradermal administration of substance P, an activator of skin mast cells, and challenge with DNP-human serum albumin after passive sensitization induced significantly greater vascular permeability in the skin of Ucp2-/- mice in vivo. Our results suggest that UCP2 can regulate mast cell activation.

Idioma originalEnglish
Páginas (desde-hasta)6313-6319
Número de páginas7
PublicaciónJournal of Immunology
Volumen183
N.º10
DOI
EstadoPublished - 15 nov 2009

Huella dactilar

Mast Cells
Histamine
Bone Marrow Cells
Histamine Release
Histidine Decarboxylase
Uncoupling Protein 2
Prostaglandin D2
Skin
Mitochondrial Proteins
Capillary Permeability
Substance P
Serum Albumin
Superoxide Dismutase
Interleukin-6
Reactive Oxygen Species
Hypersensitivity
Down-Regulation
Phosphorylation
Insulin
Cytokines

ASJC Scopus subject areas

  • Immunology

Citar esto

Tagen, M., Elorza, A., Kempuraj, D., Boucher, W., Kepley, C. L., Shirihai, O. S., & Theoharides, T. C. (2009). Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content. Journal of Immunology, 183(10), 6313-6319. https://doi.org/10.4049/jimmunol.0803422
Tagen, Michael ; Elorza, Alvaro ; Kempuraj, Duraisamy ; Boucher, William ; Kepley, Christopher L. ; Shirihai, Orian S. ; Theoharides, Theoharis C. / Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content. En: Journal of Immunology. 2009 ; Vol. 183, N.º 10. pp. 6313-6319.
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abstract = "Mast cells are immune effector cells that are involved in allergies and inflammation through the release of mediators such as histamine, PGs, and cytokines. Uncoupling protein 2 (UCP2) is a mitochondrial protein that inhibits insulin secretion from β cells, possibly through down-regulation of reactive oxygen species production. We hypothesized that UCP2 could also regulate mast cell activation. In this study, we show that mouse bone marrow mast cells (BMMCs) and human leukemic LAD2 mast cells express UCP2. BMMCs from Ucp2-/- mice exhibited greater histamine release, whereas overexpression of UCP2 in LAD2 cells reduced histamine release after both allergic and nonallergic triggers. Ucp2-/- BMMCs also had elevated histamine content and histidine decarboxylase expression. Histamine content was reduced by overexpression of UCP2 or treatment with the mitochondrial-targeted superoxide dismutase-mimetic (TBAP) tetrakis(4-benzoic acid) porphyrin manganese(III). Furthermore, Ucp2-/- BMMCs also had greater production of both IL-6 and PGD2 as well as ERK phosphorylation, which is known to regulate PG synthesis. Intradermal administration of substance P, an activator of skin mast cells, and challenge with DNP-human serum albumin after passive sensitization induced significantly greater vascular permeability in the skin of Ucp2-/- mice in vivo. Our results suggest that UCP2 can regulate mast cell activation.",
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Tagen, M, Elorza, A, Kempuraj, D, Boucher, W, Kepley, CL, Shirihai, OS & Theoharides, TC 2009, 'Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content', Journal of Immunology, vol. 183, n.º 10, pp. 6313-6319. https://doi.org/10.4049/jimmunol.0803422

Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content. / Tagen, Michael; Elorza, Alvaro; Kempuraj, Duraisamy; Boucher, William; Kepley, Christopher L.; Shirihai, Orian S.; Theoharides, Theoharis C.

En: Journal of Immunology, Vol. 183, N.º 10, 15.11.2009, p. 6313-6319.

Resultado de la investigación: Article

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T1 - Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content

AU - Tagen, Michael

AU - Elorza, Alvaro

AU - Kempuraj, Duraisamy

AU - Boucher, William

AU - Kepley, Christopher L.

AU - Shirihai, Orian S.

AU - Theoharides, Theoharis C.

PY - 2009/11/15

Y1 - 2009/11/15

N2 - Mast cells are immune effector cells that are involved in allergies and inflammation through the release of mediators such as histamine, PGs, and cytokines. Uncoupling protein 2 (UCP2) is a mitochondrial protein that inhibits insulin secretion from β cells, possibly through down-regulation of reactive oxygen species production. We hypothesized that UCP2 could also regulate mast cell activation. In this study, we show that mouse bone marrow mast cells (BMMCs) and human leukemic LAD2 mast cells express UCP2. BMMCs from Ucp2-/- mice exhibited greater histamine release, whereas overexpression of UCP2 in LAD2 cells reduced histamine release after both allergic and nonallergic triggers. Ucp2-/- BMMCs also had elevated histamine content and histidine decarboxylase expression. Histamine content was reduced by overexpression of UCP2 or treatment with the mitochondrial-targeted superoxide dismutase-mimetic (TBAP) tetrakis(4-benzoic acid) porphyrin manganese(III). Furthermore, Ucp2-/- BMMCs also had greater production of both IL-6 and PGD2 as well as ERK phosphorylation, which is known to regulate PG synthesis. Intradermal administration of substance P, an activator of skin mast cells, and challenge with DNP-human serum albumin after passive sensitization induced significantly greater vascular permeability in the skin of Ucp2-/- mice in vivo. Our results suggest that UCP2 can regulate mast cell activation.

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