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

Abstract

Lipin-1 is an Mg 2+-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.

RhFGF21 Protects Epidermal Cells against UVB-Induced Apoptosis through Activating AMPK-Mediated Autophagy

“…UVB irradiation induces skin injury through several deleterious signaling pathways, including the induction of apoptosis, inflammation, reactive oxygen species (ROS) and collagen degradation [ 23 , 34 ]. UVB irradiation induces acute inflammatory responses in skin by promoting the release of pro-inflammatory mediators such as TNFα, IL-1β, IL-6 and PGE2 [ 35 ]. Therefore, the repression of apoptosis and inflammation are critical for treating skin damage caused by UVB irradiation.…”

Evaluation of Biological Effects and Transcriptome Changes Induced by LED‐Based Narrow‐Band UVB Phototherapy

“…UVB exposure within different doses induces cell cycle arrest at the G1/S phase post-UVB irradiation (23) mediated by cyclin (24) and DNA damage (27)(28)(29). Also, UVB will stimulate the expression of several inflammation cytofactors, such as IL-1β (30), IL-6, IL-8 (31), MCP-1 and COX-2 (32), which may regulate the immune responses. Several signal pathways (such as p53, MAPK and NF-κB) are involved in the above cyto-responses.…”