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CARMA1 is critical for the development of allergic airway inflammation in a murine model of asthma.

http://www.ncbi.nlm.nih.gov/pubmed/16751370

CARMA1 has been shown to be important for Ag-stimulated activation of NF-kappaB in lymphocytes in vitro and thus could be a novel therapeutic target in inflammatory diseases such as asthma. In the present study, we demonstrate that mice with deletion in the CARMA1 gene (CARMA1(-/-)) do not develop inflammation in a murine model of asthma. Compared with wild-type controls, CARMA1(-/-) mice did not develop airway eosinophilia, had no significant T cell recruitment into the airways, and had no evidence for T cell activation in the lung or draining lymph nodes. In addition, the CARMA1(-/-) mice had significantly decreased levels of IL-4, IL-5, and IL-13, did not produce IgE, and did not develop airway hyperresponsiveness or mucus cell hypertrophy. However, adoptive transfer of wild-type Th2 cells into CARMA1(-/-) mice restored eosinophilic airway inflammation, cytokine production, airway hyperresponsiveness, and mucus production. This is the first demonstration of an in vivo role for CARMA1 in a disease process. Furthermore, the data clearly show that CARMA1 is essential for the development of allergic airway inflammation through its role in T lymphocytes, and may provide a novel means to inhibit NF-kappaB for therapy in asthma.

Pubmed ID: 16751370 RIS Download

Mesh terms: Adoptive Transfer | Allergens | Animals | Apoptosis Regulatory Proteins | Asthma | Bronchial Hyperreactivity | CARD Signaling Adaptor Proteins | Cytokines | Disease Models, Animal | Guanylate Kinase | Immunoglobulin E | Immunophenotyping | Lung | Lymph Nodes | Lymphocyte Activation | Lymphocyte Count | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Ovalbumin | Respiratory Hypersensitivity | Th2 Cells

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI27849
  • Agency: NIAID NIH HHS, Id: AI46731
  • Agency: NIDDK NIH HHS, Id: DK43351
  • Agency: NHLBI NIH HHS, Id: K08 HL072775
  • Agency: NHLBI NIH HHS, Id: K08 HL072775
  • Agency: NIDDK NIH HHS, Id: P30 DK040561
  • Agency: NIDDK NIH HHS, Id: P30 DK040561-11
  • Agency: NHLBI NIH HHS, Id: R01 HL088297

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