Luteolin targets MKK4 to attenuate particulate matter-induced MMP-1 and inflammation in human keratinocytes

Abstract

Abstract Particulate matter (PM) is an environmental pollutant that causes premature skin aging and inflammation. In the present study, we investigated the protective effects of luteolin, a bioactive flavonoid, against PM-induced skin damage in human keratinocytes (HaCaT cells). We examined the antioxidant and anti-inflammatory properties of luteolin, focusing on its ability to inhibit key markers of skin aging and inflammation, specifically matrix metalloproteinase-1 (MMP-1) and cyclooxygenase-2 (COX-2). The results demonstrated that luteolin effectively suppressed PM-induced MMP-1 and COX-2 expression and reduced the production of the proinflammatory cytokine IL-6. Mechanistically, luteolin inhibited the activation of AP-1 and NF-κB pathways and decreased reactive oxygen species (ROS) levels in HaCaT cells. Additionally, luteolin binds directly to mitogen-activated protein kinase kinase (MKK) 4, inhibiting its kinase activity and subsequently reducing the phosphorylation of JNK1/2 and p38 mitogen-activated protein kinase. These findings suggest that luteolin can mitigate PM-induced skin aging and inflammation through multiple molecular pathways, highlighting its potential as a therapeutic agent to protect skin health.