337 Downregulated Caveolin-1 expression in monocytes may contribute to the pathogenesis of psoriasis

Abstract

Caveolin-1 (CAV-1) is a membrane protein that is essential for the formation of flask-shaped membrane invaginations known as caveolae. CAV-1 regulates a variety of signaling molecules and receptors, and aberrant CAV-1 expression is involved in a variety of diseases. Our previous study showed aberrant reduction of CAV-1 in the epidermis of psoriasis patient, which leads to enhance phosphorylation of STAT3 and cytokine production, suggesting that decreased CAV-1 may contribute to the psoriatic inflammation. Not only keratinocytes, immune cells are major players in psoriasis. Migrated immune cells produce variety of effector cytokines to affect keratinocytes proliferation and induce psoriatic inflammation. The purpose of this study is to determine whether CAV-1 is involved in the leucocytes function of psoriasis and investigate their role in the pathogenesis of psoriasis. We first determined CAV-1 expression levels of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) isolated from patients with psoriasis and control subjects by quantitative PCR and immunoblotting. Immunocytochemistry and magnetic cell isolation were further conducted to identify which cells were aberrant on CAV-1 expression in PBMCs. As a result, mRNA and protein levels of CAV-1 in PBMCs and PMNs were significantly decreased in psoriasis patients compared to that in control subjects. In PBMCs, reduction of CAV-1 was observed significantly in CD14 positive monocytes. We further assessed function of CAV-1 decreased monocytes on cytokine production and their migration. RNA interference of CAV-1 in isolated monocytes represented elevated levels of IL-1b and IL-6 under LPS stimulation compared to controlled monocytes. Furthermore, migration assay revealed that CAV-1 silenced monocytes had enhanced chemotaxis activity induced by MCP-1. Our results suggest that aberrant CAV-1 expression on monocytes may be involved in the pathogenesis of psoriasis mediating cell migration and cytokine production.