Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in...

Area of Science:

• Dermatology
• Cell Biology
• Environmental Health

Background:

• Particulate matter (PMs) exposure triggers oxidative stress and inflammation.
• PMs disrupt primary cilia formation in skin cells like keratinocytes and melanocytes.
• Primary cilia play crucial roles in cellular signaling and homeostasis.

Purpose of the Study:

• To investigate the protective effects of 2-isopropylmalic acid (2-IPMA) against PM2.5-induced skin damage.
• To elucidate the role of primary ciliogenesis in mediating these protective effects.
• To evaluate 2-IPMA's impact on oxidative stress, inflammation, and matrix metalloproteinase-1 (MMP-1) expression.

Main Methods:

• Utilized dermal fibroblasts and a human 3-D-skin model.
• Assessed primary ciliogenesis, reactive oxygen species (ROS) generation, and stress kinase activation.
• Measured pro-inflammatory cytokines (IL-6, TNF-α) and MMP-1 expression.
• Employed IFT88 depletion to inhibit primary ciliogenesis.

Main Results:

• 2-IPMA promoted primary ciliogenesis and restored PM2.5-induced cilia defects in dermal fibroblasts.
• 2-IPMA inhibited excessive ROS generation and stress kinase activation.
• 2-IPMA reduced PM2.5-induced IL-6 and TNF-α production, an effect reversed by IFT88 depletion.
• 2-IPMA decreased PM2.5-induced MMP-1 expression, also reversed by IFT88 depletion.

Conclusions:

• 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.
• Primary cilia formation is a key mechanism through which 2-IPMA exerts its protective effects against PM exposure.
• 2-IPMA represents a potential therapeutic agent for mitigating skin inflammation and damage caused by particulate matter.