Abstract
Caveolin-1 (CAV-1) is the principal component of caveolae that regulates a variety of signaling molecules and receptors. Our previous study revealed CAV-1 reduction in the epidermis of patients with psoriasis, which leads to enhanced Janus kinase/signal transducer and activator of transcription activation and cytokine production, suggesting that aberrant CAV-1 expression may contribute to psoriatic inflammation. This study aimed to investigate whether abnormal modulation of CAV-1 on immune cells is involved in the pathogenesis of psoriasis. We observed that CAV-1 level in psoriasis patients was apparently reduced in peripheral blood mononuclear cells (PBMCs) and it was prominent in CD14+ monocytes. CAV-1 silencing in monocytes represented elevated levels of interleukin (IL)-1β and IL-6, and those had enhanced chemotaxis activity. In a murine model of psoriasis-like inflammation induced by imiquimod, we observed a significant CAV-1 reduction in PBMCs. Systemic administration of CAV-1 scaffolding domain peptide significantly improved the skin phenotype with less macrophage infiltration. Taken together, aberrant CAV-1 expression in monocytes may be involved in the pathogenesis of psoriasis.
Highlights
Psoriasis vulgaris is a chronic immune-mediated inflammatory skin disease characterized by scaly papulosquamous plaque lesions[1]
peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were isolated from patients with psoriasis vulgaris, who had no history of biologic use and no current use of immunosuppressant, and from healthy subjects
Recovery of CAV-1 level in PBMCs was observed as clinical improvement by treatments (Fig. 1e, P = 0.002 in total, P = 0.016 in patients treated with tumour necrosis factor (TNF)-α inhibitors)
Summary
Psoriasis vulgaris is a chronic immune-mediated inflammatory skin disease characterized by scaly papulosquamous plaque lesions[1]. We previously reported a significant reduction of CAV-1 in the epidermis of patients with psoriasis. A reduction of CAV-1 induces activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in psoriatic inflammation. This activation leads to further keratinocyte proliferation and cytokine/chemokine production[3]. CAV-1 inhibits the expression of pro-inflammatory cytokines from macrophages by regulating the activation of mitogen-activated protein kinase (MAPK) family members[8]. We hypothesized that abnormal CAV-1 level in keratinocytes and in leukocytes may be involved in the pathogenesis of psoriasis. We evaluated CAV-1 levels in leukocytes of patients with psoriasis and investigated their roles in the pathogenesis of psoriasis
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