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UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes

Experimental & Molecular Medicine 2020년 52권 2호 p.9 ~ 9
 ( Chae Min-Jung ) - Amorepacific Corporation R&D Center

손의동 ( Son Eui-Dong ) - Amorepacific Corporation R&D Center
배일홍 ( Bae Il-Hong ) - Amorepacific Corporation R&D Center
 ( Cho Eun-Gyung ) - Amorepacific Corporation R&D Center
 ( Kim Hyoung-June ) - Amorepacific Corporation R&D Center
정지용 ( Jung Ji-Yong ) - Amorepacific Corporation R&D Center

Abstract


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.

키워드

Interleukins; Lipid signalling
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