GLP-1 receptor agonist impairs keratinocytes inflammatory signals by activating AMPK

Purpose: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, is an antidiabetic drug. It has been shown to improve the Psoriasis Area and Severity Index (PASI) in patients with type 2 diabetes and psoriasis in clinical practice, but the mechanism remains somewhat unclear. We used lipopolysaccharides (LPS) to induce inflammatory response in keratinocytes and explore the mechanism. Methods: The HaCat cells were incubated with LPS for 16 h and then were treated with liraglutide for 30 min. Cell viability was testing by CCK-8 assay. GLP-1Rs and intracellular signaling pathways were identified by Western blot. The migration of macrophage was detecting by trans-well assay. Results: Liraglutide decreased cell viability in the HaCat cells. Liraglutide restrained the migration of macrophage to the HaCat cells. LPS elevated not only the protein abundance of phospho-IKK alpha/beta S176/S180, phospho-NF-kappa B p65, phospho-JAK2, phospho-STAT3 and SOCS3, but also the levels of TNF-alpha and IL-6 in the HaCat cells. These effects of LPS were reversed by liraglutide. In addition, liraglutide increased phosphorylation of AMPK. The AMPK inhibitor Compound (CC) impaired liraglutide-inhibited p-NF-kappa B p65 and p-STAT3. Conclusions: GLP-1 impaired keratinocytes inflammatory signals by activating AMPK and restrained macrophage migration.