Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced murine model of asthma.
Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced murine model of asthma.
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DOI：
10.1186/1465-9921-8-90
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发表时间：
2007-12-04
影响因子：
5.8
通讯作者：
Reddy RC
中科院分区：
文献类型：
--
作者：
Narala VR;Ranga R;Smith MR;Berlin AA;Standiford TJ;Lukacs NW;Reddy RC
虽然糖皮质激素是目前最有效的哮喘治疗方法，但相关的副作用限制了人们使用它们的热情。过氧化物酶体增殖物激活受体-γ（PPAR-γ）激活剂包括合成的噻唑烷二酮（TZD），其表现出抗炎作用，表明其在疾病如哮喘中是有用的。然而，TZDs调节哮喘反应的能力与糖皮质激素相比如何仍然不清楚，因为这两种核受体激动剂从未同时研究过。此外，在涉及通常与人类哮喘相关的过敏原的模型中，从未检查过PPAR-γ激动剂的作用。我们在蟑螂过敏原（CRA）诱导的哮喘小鼠模型中比较了PPAR-γ激动剂吡格列酮（PIO）与糖皮质激素受体激动剂地塞米松（DEX）的有效性。在通过鼻内滴注变应原致敏CRA和气道定位后，Balb/c小鼠以48小时间隔用鼻内CRA激发两次。在整个气道CRA暴露期间，给予PIO（25 mg/kg/d）、DEX（1 mg/kg/d）或溶媒。PIO和DEX在降低气道高反应性、炎性细胞的肺募集、血清IgE和IL-4、IL-5、TNF-α、TGF-β、RANTES、嗜酸性粒细胞趋化因子、MIP 3-α、Gob-5和Muc 5-ac的肺水平方面表现出相似的能力。同样，气管内施用含有组成型活性的PPAR-γ表达构建体的腺病毒阻断了CRA对Gob-5和Muc 5-ac的诱导。鉴于PIO显示的有效性，我们得出结论，PPAR-γ激动剂作为人类哮喘的潜在治疗方法值得研究。
While glucocorticoids are currently the most effective therapy for asthma, associated side effects limit enthusiasm for their use. Peroxisome proliferator-activated receptor-γ (PPAR-γ) activators include the synthetic thiazolidinediones (TZDs) which exhibit anti-inflammatory effects that suggest usefulness in diseases such as asthma. How the ability of TZDs to modulate the asthmatic response compares to that of glucocorticoids remains unclear, however, because these two nuclear receptor agonists have never been studied concurrently. Additionally, effects of PPAR-γ agonists have never been examined in a model involving an allergen commonly associated with human asthma. We compared the effectiveness of the PPAR-γ agonist pioglitazone (PIO) to the established effectiveness of a glucocorticoid receptor agonist, dexamethasone (DEX), in a murine model of asthma induced by cockroach allergen (CRA). After sensitization to CRA and airway localization by intranasal instillation of the allergen, Balb/c mice were challenged twice at 48-h intervals with intratracheal CRA. Either PIO (25 mg/kg/d), DEX (1 mg/kg/d), or vehicle was administered throughout the period of airway CRA exposure. PIO and DEX demonstrated similar abilities to reduce airway hyperresponsiveness, pulmonary recruitment of inflammatory cells, serum IgE, and lung levels of IL-4, IL-5, TNF-α, TGF-β, RANTES, eotaxin, MIP3-α, Gob-5, and Muc5-ac. Likewise, intratracheal administration of an adenovirus containing a constitutively active PPAR-γ expression construct blocked CRA induction of Gob-5 and Muc5-ac. Given the potent effectiveness shown by PIO, we conclude that PPAR-γ agonists deserve investigation as potential therapies for human asthma.
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影响因子：
6
作者：
Hammad, H;de Heer, HJ;Lambrecht, BN
通讯作者：
Lambrecht, BN
影响因子：
64.8
作者：
Jiang, CY;Ting, AT;Seed, B
通讯作者：
Seed, B
影响因子：
25.7
作者：
Akahori, Takahiro;Sho, Masayuki;Nakajima, Yoshiyuki
通讯作者：
Nakajima, Yoshiyuki
影响因子：
6.1
作者：
Eum, SY;Creminon, C;Vargaftig, BB
通讯作者：
Vargaftig, BB
DOI：
10.1152/ajplung.00433.2003
发表时间：
2004-09-01
影响因子：
4.9
作者：
Kim, J;McKinley, L;Remick, DG
通讯作者：
Remick, DG