UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes.,Experimental & Molecular Medicine

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UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2020-02-21 , DOI: 10.1038/s12276-020-0388-y
Minjung Chae ₁ , Eui Dong Son ₁ , Il-Hong Bae ₁ , Eun-Gyung Cho ₁ , Hyoung-June Kim ₁ , Ji-Yong Jung ₁

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Lipin-1 is an Mg2+-dependent phosphatidate phosphatase (PAP1) that catalyzes a critical step in the synthesis of glycerophospholipids and is also a cotranscriptional regulator. The role of lipin-1 in the regulation of inflammatory responses has been extensively studied in various cell types but not in skin cells. In the present study, the function of lipin-1 in UVB-induced proinflammatory responses was assessed in normal human epidermal keratinocytes (NHEKs). UVB radiation downregulated lipin-1 expression. Lipin-1 inhibition was mediated by UVB-dependent sterol-response element binding protein-1 (SREBP-1) inhibition. The UVB-dependent inhibition of lipin-1 and SREBP-1 was mediated by AMPK activation. UVB-induced activation of JNK was dependent on AMPK activation and mediated lipin-1 inhibition. Prevention of UVB-mediated lipin-1 repression by introducing a lipin-1 expression vector stimulated IL-6 and IL-8 production, suggesting that lipin-1 inhibition attenuates UVB-induced IL-6 and IL-8 production. The downregulation of lipin-1 ameliorated UVB-induced NF-ĸB phosphorylation, which might be attributed to the suppression of UVB-induced accumulation of free fatty acids (FFAs). Pharmacological inhibition of PAP1 with propranolol suppressed UVB-induced production of IL-6 and IL-8 in NHEKs and reconstituted human skin models. Taken together, lipin-1 is downregulated by exposure to UVB radiation, which confers protection against UVB-induced proinflammatory responses; therefore, the inhibition of lipin-1 is a potential strategy for photoaging.

中文翻译：

UVB依赖的lipin-1抑制作用可防止人类角质形成细胞的促炎反应。

Lipin-1是一种Mg2 +依赖性磷脂酰磷酸酶（PAP1），可催化甘油磷脂合成中的关键步骤，并且还是共转录调节剂。在多种细胞类型中而不是在皮肤细胞中已经广泛研究了脂蛋白-1在调节炎症反应中的作用。在本研究中，在正常人表皮角质形成细胞（NHEK）中评估了脂蛋白1在UVB诱导的促炎反应中的功能。UVB辐射下调lipin-1表达。脂蛋白1抑制是由UVB依赖的固醇-反应元件结合蛋白1（SREBP-1）抑制介导的。脂肪蛋白1和SREBP-1的UVB依赖性抑制是由AMPK激活介导的。UVB诱导的JNK激活取决于AMPK激活和介导的脂蛋白1抑制。通过引入脂蛋白-1表达载体刺激IL-6和IL-8产生来预防UVB介导的lipin-1抑制，表明脂蛋白-1抑制作用减弱了UVB诱导的IL-6和IL-8产生。lipin-1的下调改善了UVB诱导的NF-ĸB磷酸化，这可能归因于UVB诱导的游离脂肪酸（FFA）积累的抑制。普萘洛尔对PAP1的药理抑制作用抑制了UVB诱导的NHEKs和重建的人类皮肤模型中IL-6和IL-8的产生。综上所述，脂蛋白-1通过暴露于UVB辐射而被下调，从而赋予针对UVB诱导的促炎反应的保护；因此，抑制脂质1是光老化的潜在策略。提示脂蛋白1抑制可减弱UVB诱导的IL-6和IL-8产生。lipin-1的下调改善了UVB诱导的NF-ĸB磷酸化，这可能归因于UVB诱导的游离脂肪酸（FFA）积累的抑制。普萘洛尔对PAP1的药理抑制作用抑制了UVB诱导的NHEKs和重建的人类皮肤模型中IL-6和IL-8的产生。综上所述，通过暴露于UVB辐射，脂蛋白1会下调，从而赋予针对UVB诱导的促炎反应的保护；因此，抑制脂质1是光老化的潜在策略。提示脂蛋白1抑制可减弱UVB诱导的IL-6和IL-8产生。lipin-1的下调改善了UVB诱导的NF-ĸB磷酸化，这可能归因于UVB诱导的游离脂肪酸（FFA）积累的抑制。普萘洛尔对PAP1的药理抑制作用抑制了UVB诱导的NHEKs和重建的人类皮肤模型中IL-6和IL-8的产生。综上所述，脂蛋白-1通过暴露于UVB辐射而被下调，从而赋予针对UVB诱导的促炎反应的保护；因此，抑制脂质1是光老化的潜在策略。这可能归因于抑制UVB诱导的游离脂肪酸（FFA）积累。普萘洛尔对PAP1的药理抑制作用抑制了UVB诱导的NHEKs和重建的人类皮肤模型中IL-6和IL-8的产生。综上所述，通过暴露于UVB辐射，脂蛋白1会下调，从而赋予针对UVB诱导的促炎反应的保护；因此，抑制脂质1是光老化的潜在策略。这可能归因于抑制UVB诱导的游离脂肪酸（FFA）积累。普萘洛尔对PAP1的药理抑制作用抑制了UVB诱导的NHEKs和重建的人类皮肤模型中IL-6和IL-8的产生。综上所述，脂蛋白-1通过暴露于UVB辐射而被下调，从而赋予针对UVB诱导的促炎反应的保护；因此，抑制脂质1是光老化的潜在策略。

更新日期：2020-02-21

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