Kallikrein expression and cathelicidin processing are independently controlled in keratinocytes by calcium, vitamin D(3), and retinoic acid.
Kallikrein expression and cathelicidin processing are independently controlled in keratinocytes by calcium, vitamin D(3), and retinoic acid.
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DOI：
10.1038/jid.2009.435
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发表时间：
2010-05
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Cathelicidin在皮肤中具有双重功能，作为先天性抗生素和作为疾病如红斑痤疮和牛皮癣的免疫调节剂。丝氨酸蛋白酶激肽释放酶5（KLK 5）和激肽释放酶7（KLK 7）控制皮肤中凯萨林菌素前体的酶促加工，并调节这些肽的最终形式的最终功能。我们分析了控制正常人表皮角质形成细胞中KLK 5和KLK 7表达的因素，以更好地了解这些因素如何影响凯萨林菌素的加工和功能。细胞外钙诱导的KLK 5和KLK 7 mRNA表达和蛋白质释放以时间依赖性方式增加，类似于诱导分化标志物，如角蛋白10和外皮蛋白。然而，1，25（OH）2维生素D3，9-顺式视黄酸（RA），和13-顺式RA也诱导KLK，但KLK诱导的时间和模式为每一个是不同的，不同的分化标志物的变化。蛋白酶活性的增加和凯萨林菌素的差异加工伴随着KLK表达的增加。这些发现表明KLK的表达和活性处于精细控制之下，并且可以明显地受到诸如分化、钙、维生素D和RA的变量的影响。因此，这些变量可以进一步控制皮肤中抗微生物肽的功能。
Cathelicidin has dual functions in the skin, acting as an innate antibiotic and as an immunomodulator in diseases such as rosacea and psoriasis. The serine proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7) control enzymatic processing of cathelicidin precursor in the skin and regulate the eventual function of the final forms of these peptides. We analyzed factors that control expression of KLK5 and KLK7 in normal human epidermal keratinocytes to better understand how these may influence cathelicidin processing and function. Increased extracellular calcium-induced KLK5 and KLK7 mRNA expression and protein release in a time-dependent manner that is similar to induction of differentiation markers such as keratin 10 and involucrin. However, 1,25(OH)2 vitamin D3, 9-cis retinoic acid (RA), and 13-cisRA also induced the KLKs, but the timing and pattern of KLK induction for each were different and distinct from changes in differentiation markers. Increased protease activity and differential processing of cathelicidin accompanied increased KLK expression. These findings show that the expression and activity of KLK are under fine control and can be distinctly influenced by variables such as differentiation, calcium, vitamin D, and RA. Thus, these variables may further control the functions of antimicrobial peptides in the skin.
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DOI：
10.1006/mcbr.1999.0165
发表时间：
1999-08-01
期刊：
Molecular cell biology research communications : MCBRC
影响因子：
--
作者：
Poumay, Y;Herphelin, F;Pittelkow, M R
通讯作者：
Pittelkow, M R
影响因子：
6.5
作者：
Braff, MH;Di Nardo, A;Gallo, RL
通讯作者：
Gallo, RL
影响因子：
64.8
作者：
Nizet, V;Ohtake, T;Gallo, RL
通讯作者：
Gallo, RL
影响因子：
6.5
作者：
Hansson, L;Bäckman, A;Egelrud, T
通讯作者：
Egelrud, T
影响因子：
6.5
作者：
Ishida-Yamamoto, A;Deraison, C;Hovnanian, A
通讯作者：
Hovnanian, A