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Sci Transl Med:激素在抗击皮肤感染中发挥关键作用

2012-05-24 Beyond 生物谷

抗菌肽(AMPS)是由皮肤产生的能抵御感染致病微生物的分子。维生素D在这些抗菌肽的产生以及身体的整体免疫反应中发挥重要作用,但近日,美国加州大学圣迭戈学校医学院的科学家们证实了一种激素对维持钙稳态和骨骼健康也是至关重要的,这种激素能提高AMP的表达时、弥补维生素D水平不足。 这一研究发现发表在5月23日的Science Translational Medicine 杂志上,这项研究更充分地解释了

抗菌肽(AMPS)是由皮肤产生的能抵御感染致病微生物的分子。维生素D在这些抗菌肽的产生以及身体的整体免疫反应中发挥重要作用,但近日,美国加州大学圣迭戈学校医学院的科学家们证实了一种激素对维持钙稳态和骨骼健康也是至关重要的,这种激素能提高AMP的表达时、弥补维生素D水平不足。

这一研究发现发表在5月23日的Science Translational Medicine 杂志上,这项研究更充分地解释了免疫系统在不同情况下是如何发挥功能的,并提出了新的治疗感染的途径,这种新途径也许将来可以作为抗生素治疗的替代疗法。

维生素D对免疫的功效一直以来备受争议。在体外培养细胞的研究中,脂溶性维生素能带来强有力的免疫利益,但在人体和动物模型的反复研究中,结果却一直不一致:膳食中维生素D水平低的人不会受到更多的感染。其中原因一直不知,膳食中维生素D水平低的人免疫反应普遍依然良好。

小鼠模型和人体细胞培养研究工作中,Gallo和同事发现了其中原因:当膳食维生素D水平低时,甲状旁腺激素(PTH)的产生(通常有助于调节血液中的钙水平)是上升的。PTH或相关的肽称为PHTrP,其能增加AMPs如抗菌肽的表达。

加州大学圣地亚哥分校的皮肤病科主任Richard L. Gallo医学博士说:没有人怀疑甲状旁腺或甲状旁腺素相关肽的免疫作用。这一研究结果可能有助于解决一些有关维生素D对免疫功效的争议。

例如维生素D与阳光照射的两者之间的关系。阳光触发维生素D的产生已在一些研究中得到证实,但是否增加心血管疾病和癌症的风险,这一点还未得到证实。另一方面,太阳照射过多,可以增加维生素D,进而增加皮肤癌的风险。

Gallo说:因为阳光是一种致癌物质,照射过多并不好。当从饮食和阳光照射中获得的维生素D水平低时,PTH会上升。

研究人员表示:尽管还有许多研究工作有待完成,其中就包括人体研究。但PTH或PTHrP最终可能会成为一个有效的抗生素治疗,这种疗法并不会带来抗生素抗药性的风险。

这项研究部分资助由美国国家过敏和传染病研究所、国立卫生研究院(NIH)提供。(生物谷:Bioon.com)

doi:10.1126/scitranslmed.3003759
PMC:
PMID:

PTH/PTHrP and Vitamin D Control Antimicrobial Peptide Expression and Susceptibility to Bacterial Skin Infection

Beda Muehleisen, Daniel D. Bikle, Carlos Aguilera, Douglas W. Burton, George L. Sen, Leonard J. Deftos, and Richard L. Gallo.

The production of antimicrobial peptides is essential for protection against a wide variety of microbial pathogens and plays an important role in the pathogenesis of several diseases. The mechanisms responsible for expression of antimicrobial peptides are incompletely understood, but a role for vitamin D as a transcriptional inducer of the antimicrobial peptide cathelicidin has been proposed. We show that 1,25-dihydroxyvitamin D3 (1,25-D3) acts together with parathyroid hormone (PTH), or the shared amino-terminal domain of PTH-related peptide (PTHrP), to synergistically increase cathelicidin and immune defense. Administration of PTH to mouse skin decreased susceptibility to skin infection by group A Streptococcus. Mice on dietary vitamin D3 restriction that responded with an elevation in PTH have an increased risk of infection if they lack 1,25-D3. These results identify PTH/PTHrP as a variable that serves to compensate for inadequate vitamin D during activation of antimicrobial peptide production.

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    2012-10-18 bsmagic9140
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