Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling, resulting in a substantial economic burden on both patients and society. Deguelin, a constituent of the Leguminosae family, exhibits anti-proliferative and anti-inflammatory activities in cancer mice models via inhibiting phosphatidylinositol 3-kinases and the NF-kappa B pathway. We demonstrated that deguelin effectively reduced OVA-induced inflammatory cell recruitment, decreased lung tissue inflammation and mucus production, suppressed airway hyperresponsiveness, and inhibited serum immunoglobulin and Th2 cytokine levels in a dose-dependent manner in asthmatic mice. In addition, we found that deguelin reduced inflammatory gene expressions both in vivo and in vitro, which were closely associated with activation of the NF-kappa B signaling pathway. Thus, we further explored the underlying mechanisms of deguelin in normal human bronchial epithelial cells (BEAS-2B). Our results suggested that deguelin inhibited NF-kappa B binding activity by enhancing the ability of I kappa Ba to maintain NF-kappa B in an inactive form in the cytoplasm and preventing the TNF-alpha induced translocation of p65 to the nucleus. In conclusion, our research indicates that deguelin attenuates allergic airway inflammation via inhibition of NF-.B pathway in mice model and may act as a potential therapeutic agent for patients with allergic airway inflammation.
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Causton, Benjamin
;
Ramadas, Ravisankar A.
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机构:
Merck Res Labs, Boston, MA 02115 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Ramadas, Ravisankar A.
;
Cho, Josalyn L.
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Cho, Josalyn L.
;
Jones, Khristianna
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Jones, Khristianna
;
Pardo-Saganta, Ana
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h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Pardo-Saganta, Ana
;
Rajagopal, Jayaraj
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机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Rajagopal, Jayaraj
;
Xavier, Ramnik J.
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Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Xavier, Ramnik J.
;
Medoff, Benjamin D.
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机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
机构:
Univ Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, CanadaUniv Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
Cockcroft, Donald W.
;
Davis, Beth E.
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机构:
Univ Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, CanadaUniv Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
机构:
Thomas Jefferson Univ, Philadelphia, PA 19107 USA
Nemours AI duPont Hosp Children, Div Allergy & Immunol, Wilmington, DE USAThomas Jefferson Univ, Philadelphia, PA 19107 USA
Eng, Stephanie S.
;
DeFelice, Magee L.
论文数: 0引用数: 0
h-index: 0
机构:
Thomas Jefferson Univ, Philadelphia, PA 19107 USA
Nemours AI duPont Hosp Children, Div Allergy & Immunol, Wilmington, DE USAThomas Jefferson Univ, Philadelphia, PA 19107 USA
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Causton, Benjamin
;
Ramadas, Ravisankar A.
论文数: 0引用数: 0
h-index: 0
机构:
Merck Res Labs, Boston, MA 02115 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Ramadas, Ravisankar A.
;
Cho, Josalyn L.
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Cho, Josalyn L.
;
Jones, Khristianna
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Jones, Khristianna
;
Pardo-Saganta, Ana
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Pardo-Saganta, Ana
;
Rajagopal, Jayaraj
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Rajagopal, Jayaraj
;
Xavier, Ramnik J.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Xavier, Ramnik J.
;
Medoff, Benjamin D.
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USA
Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Charlestown, MA 02129 USAMassachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA
机构:
Univ Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, CanadaUniv Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
Cockcroft, Donald W.
;
Davis, Beth E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, CanadaUniv Saskatchewan, Div Respirol Crit Care & Sleep Med, Dept Med, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
机构:
Thomas Jefferson Univ, Philadelphia, PA 19107 USA
Nemours AI duPont Hosp Children, Div Allergy & Immunol, Wilmington, DE USAThomas Jefferson Univ, Philadelphia, PA 19107 USA
Eng, Stephanie S.
;
DeFelice, Magee L.
论文数: 0引用数: 0
h-index: 0
机构:
Thomas Jefferson Univ, Philadelphia, PA 19107 USA
Nemours AI duPont Hosp Children, Div Allergy & Immunol, Wilmington, DE USAThomas Jefferson Univ, Philadelphia, PA 19107 USA