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

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. Reduced production and activity of an enzyme in skin cells helps protect them from damage caused by exposure to ultra-violet light. Minjung Chae and colleagues at the Amorepacific Corporation in Yongin, South Korea, identified an anti-inflammatory effect caused by the reduction in expression of the enzyme lipin-1 when skin cells are exposed to UVB radiation. These ultra-violet rays are associated with aging and increased risk of skin cancer. Lipin-1 is involved in making glycerophospholipid molecules, which are key components of the membranes surrounding and inside cells. Identifying the enzyme’s significance for inflammation in skin cells extends previous similar findings with other cell types. The research also uncovered aspects of the molecular mechanisms mediating the skin cell response. Inhibiting lipin-1 activity might reduce the damage sunlight causes to skin.