The multifunctional host defense peptide SPLUNC1 is critical for homeostasis of the mammalian upper airway.
The multifunctional host defense peptide SPLUNC1 is critical for homeostasis of the mammalian upper airway.
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DOI：
10.1371/journal.pone.0013224
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发表时间：
2010-10-07
期刊：
影响因子：
3.7
通讯作者：
Bakaletz LO
中科院分区：
文献类型：
--
作者：
McGillivary G;Bakaletz LO
中耳炎(OM)是一种高度流行的儿科疾病，由鼻咽正常菌群沿咽鼓管上升进入中耳引起。由于OM是一种偶然性疾病，因此增加对在上呼吸道起作用的免疫系统成分的了解并帮助预防这种疾病是至关重要的。SPLunc1是一种抗菌宿主防御肽，被认为通过杀菌和非杀菌机制对呼吸道的健康做出贡献。我们利用小干扰RNA(SiRNA)技术下调人SPLunc1的栗鼠同源基因(CSPLunc1)的表达，以开始确定该蛋白在预防OM中所起的作用。我们发现，在所测试的条件下，下调cSPLUN1的表达并不影响不可分型的流感嗜血杆菌在龙猫中耳中的存活，流感嗜血杆菌是OM的主要病原体。相反，cSPLunc1的表达对于维持中耳压力和有效的粘液纤毛清除是必不可少的，而粘液纤毛清除是管鼓室的关键防御机制。总而言之，我们的数据提供了第一个活体证据，证明cSPLunc1功能维持上呼吸道的动态平衡，从而对保护中耳至关重要。
Otitis media (OM) is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the Eustachian tube and enter the middle ear. As OM is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. SPLUNC1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bactericidal mechanisms. We used small interfering RNA (siRNA) technology to knock down expression of the chinchilla ortholog of human SPLUNC1 (cSPLUNC1) to begin to determine the role that this protein played in prevention of OM. We showed that knock down of cSPLUNC1 expression did not impact survival of nontypeable Haemophilus influenzae, a predominant causative agent of OM, in the chinchilla middle ear under the conditions tested. In contrast, expression of cSPLUNC1 was essential for maintenance of middle ear pressure and efficient mucociliary clearance, key defense mechanisms of the tubotympanum. Collectively, our data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear.
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影响因子：
7.3
作者：
Bingle, L;Cross, SS;Bingle, CD
通讯作者：
Bingle, CD
影响因子：
3.6
作者：
Kaplan, B;Wandstrat, TL;Cunningham, JR
通讯作者：
Cunningham, JR
影响因子：
3.9
作者：
Ghafouri, B;Kihlström, E;Lindahl, M
通讯作者：
Lindahl, M
影响因子：
2.6
作者：
Jung, HH;Chae, SW;Hwang, SJ
通讯作者：
Hwang, SJ
DOI：
10.1016/s0167-4781(00)00196-2
发表时间：
2000-10-02
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Bingle, CD;Bingle, L
通讯作者：
Bingle, L