Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids.
Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids.
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DOI：
10.1371/journal.pone.0044606
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lavoie JP
中科院分区：
文献类型：
--
作者：
Hirsch G;Lavoie-Lamoureux A;Beauchamp G;Lavoie JP
一般认为，与其他炎症细胞相比，中性粒细胞对糖皮质激素的反应较差。据报道，由这些药物介导的人类中性粒细胞存活率的增加在一定程度上支持了这一说法。然而，最近的研究表明，地塞米松对马外周血中性粒细胞有很强的抗炎作用。中性粒细胞和其他白细胞中糖皮质激素作用的比较研究很少有报道，不能排除中性粒细胞对这些药物相对不敏感的可能性。我们评估了马和人外周血中性粒细胞和去中性粒细胞的糖皮质激素反应性。从6匹健康马和4名健康人的血液中分离出中性粒细胞和去中性粒细胞。单独或不加内毒素(10 0 ng/m L)或与氢化可的松、强的松龙或地塞米松(10−8M和10−6M)联合孵育5h。定量聚合酶链式反应检测IL-1β、肿瘤坏死因子-α、IL-8、谷氨酰胺合成酶和GR-α基因的表达。马中性粒细胞在加或不加三种糖皮质激素的情况下孵育20h，用流式细胞仪和光镜观察细胞存活率。我们发现糖皮质激素在细胞群体和物种中都下调了内毒素诱导的促炎基因的表达。这些药物还显著增加了这两个马细胞群体中谷氨酰胺合成酶基因的表达。在两个物种中，细胞群体之间的糖皮质激素反应的大小通常是相似的。我们还发现，地塞米松对人和马中性粒细胞中的促炎基因表达具有类似的抑制作用。正如在其他物种中所报道的那样，糖皮质激素显著提高了马中性粒细胞的存活率。糖皮质激素对中性粒细胞和其他血液白细胞产生类似程度的基因组效应。我们推测，一些慢性中性粒细胞疾病，如严重哮喘或COPD，对糖皮质激素的反应差，并不是因为这些药物相对缺乏对中性粒细胞促炎细胞因子表达的抑制。
Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out. We assessed glucocorticoid-responsiveness in equine and human peripheral blood neutrophils and neutrophil-depleted leukocytes. Blood neutrophils and neutrophil-depleted leukocytes were isolated from 6 healthy horses and 4 human healthy subjects. Cells were incubated for 5 h with or without LPS (100 ng/mL) alone or combined with hydrocortisone, prednisolone or dexamethasone (10−8 M and 10−6 M). IL-1β, TNF-α, IL-8, glutamine synthetase and GR-α mRNA expression was quantified by qPCR. Equine neutrophils were also incubated for 20 h with or without the three glucocorticoids and cell survival was assessed by flow cytometry and light microscopy on cytospin preparations. We found that glucocorticoids down-regulated LPS-induced pro-inflammatory mRNA expression in both cell populations and species. These drugs also significantly increased glutamine synthetase gene expression in both equine cell populations. The magnitude of glucocorticoid response between cell populations was generally similar in both species. We also showed that dexamethasone had a comparable inhibitory effect on pro-inflammatory gene expression in both human and equine neutrophils. As reported in other species, glucocorticoids significantly increase the survival in equine neutrophils. Glucocorticoids exert genomic effects of similar magnitude on neutrophils and on other blood leukocytes. We speculate that the poor response to glucocorticoids observed in some chronic neutrophilic diseases such as severe asthma or COPD is not explained by a relative lack of inhibition of these drugs on pro-inflammatory cytokines expression in neutrophils.
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DOI：
10.1152/ajplung.00135.2009
发表时间：
2010-10-01
影响因子：
4.9
作者：
Lavoie-Lamoureux, Anouk;Moran, Kantuta;Lavoie, Jean-Pierre
通讯作者：
Lavoie, Jean-Pierre
影响因子：
2.6
作者：
Garosi, L;McConnell, JF;Schatzberg, SJ
通讯作者：
Schatzberg, SJ
影响因子：
2.2
作者：
Joubert, P;Silversides, DW;Lavoie, JP
通讯作者：
Lavoie, JP
影响因子：
1
作者：
Lavoie, JP;Léguillette, R;Hickey, GJ
通讯作者：
Hickey, GJ
影响因子：
24.3
作者：
Langereis, J. D.;Oudijk, E-J. D.;Ulfman, L. H.
通讯作者：
Ulfman, L. H.