MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac (Retracted article. See vol. 309, pg. L 750, 2015)
MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac (Retracted article. See vol. 309, pg. L 750, 2015)
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DOI：
10.1152/ajplung.00067.2010
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发表时间：
2010-09-01
影响因子：
4.9
通讯作者：
Voynow, Judith A.
中科院分区：
文献类型：
--
作者：
Foster, W. Michael;Adler, Kenneth B.;Voynow, Judith A.
Foster WM, Adler KB, Crews AL, Potts EN, Fischer BM, Voynow JA。marks相关肽在体内调节气道Muc5ac的分泌。[J] .中国生物医学工程学报，2016,31(2):444 - 444。首次发表于2010年6月11日；doi: 10.1152 / ajplung.00067.2010。在出现杯状细胞化生和炎症的中性粒细胞弹性酶诱导的支气管炎小鼠模型中，我们研究了气管内灌注MANS肽（一种与肉芽酰基化富丙氨酸C激酶底物（MARCKS）的NH2端相同的肽）对粘蛋白气道分泌、炎症和气道反应性的影响。为了诱导气道粘液细胞化生，雄性BALB/c小鼠在第1、4和7天重复使用丝氨酸蛋白酶、中性粒细胞弹性蛋白酶。第11天，当杯状细胞化生完全发育，促炎细胞因子谱达到最大值时，在气管内注入MANS或错意控制肽（RNS）后，将动物暴露于雾化的甲胆碱。MANS，而非RNS，减弱了甲基苯丙胺刺激的主要呼吸道粘蛋白Muc5ac的分泌（减少50%）。同时，弹性酶诱导的促炎细胞因子通常在支气管肺泡灌洗（BAL）中恢复，包括KC、IL-1 β、IL-6、MCP-1和TNF α，被MANS肽降低（平均水平下降50-60%）。继MANS对粘蛋白分泌和炎症的影响之后，通过强迫振荡技术表征了机械肺功能对5 -羟色胺累积气溶胶刺激的气道反应性。在这个气道高分泌模型中，MANS肽也被发现有效地减弱气道对血清素的高反应性。总的来说，这些发现支持这样一个概念，即即使在杯状细胞化生重塑的气道上皮中，在粘蛋白高分泌状态下，通过MANS肽的MARCKS蛋白功能的外源性衰减也会减少气道粘蛋白分泌、炎症和高反应性。
Foster WM, Adler KB, Crews AL, Potts EN, Fischer BM, Voynow JA. MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac. Am J Physiol Lung Cell Mol Physiol 299: L345-L352, 2010. First published June 11, 2010; doi:10.1152/ajplung.00067.2010.-In a mouse model of neutrophil elastase-induced bronchitis that exhibits goblet cell metaplasia and inflammation, we investigated the effects of intratracheal instillation of the MANS peptide, a peptide identical to the NH2 terminus of the myristoylated alanine-rich C kinase substrate (MARCKS) on mucin protein airway secretion, inflammation, and airway reactivity. To induce mucus cell metaplasia in the airways, male BALB/c mice were treated repetitively with the serine protease, neutrophil elastase, on days 1, 4, and 7. On day 11, when goblet cell metaplasia was fully developed and profiles of proinflammatory cytokines were maximal, the animals were exposed to aerosolized methacholine after intratracheal instillation of MANS or a missense control peptide (RNS). MANS, but not RNS, attenuated the methacholine-stimulated secretion of the major respiratory mucin protein, Muc5ac (50% reduction). Concurrently, elastase-induced proinflammatory cytokines typically recovered in bronchoalveolar lavage (BAL), including KC, IL-1 beta, IL-6, MCP-1, and TNF alpha, were reduced by the MANS peptide (mean levels decreased 50-60%). Secondary to the effects of MANS on mucin secretion and inflammation, mechanical lung function by forced oscillation technique was characterized with respect to airway reactivity in response to cumulative aerosol stimulation with serotonin. The MANS peptide was also found to effectively attenuate airway hyperresponsiveness to serotonin in this airway hypersecretory model. Collectively, these findings support the concept that even in airway epithelia remodeled with goblet cell metaplasia and in a state of mucin hypersecretion, exogenous attenuation of function of MARCKS protein via the MANS peptide decreases airway mucin secretion, inflammation, and hyperreactivity.