CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma

Abstract

The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1α, IL-1β, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature.

Expression Levels of Inflammatory and Oxidative Stress-Related Genes in Skin Biopsies and Their Association with Pityriasis Alba

“…The stratified architecture of the skin, and its antioxidant systems and melanogenesis capacity, are the major defense mechanisms against ultraviolet radiation (UVr) [ 18 ]. Considering that UV exposition of the skin promotes an acute inflammatory response and an increase of OS in other skin diseases [ 8 , 9 , 14 , 19 , 20 ], we evaluated the expression levels of inflammatory and OS-related genes in skin biopsies and their association with PA. Our results showed differences in the ΔCq values of pro-inflammatory cytokine genes ( IL-6 and INFγ ) and antioxidant-related genes ( SOD1 and HMOX1 ) between skin biopsies with and without lesions. Compared with healthy skin, the expression levels of these genes were predominantly downregulated in lesions.…”

“…Inflammatory cytokines, produced by keratinocytes or other immune cells, are increased after UV exposition and are closely related to changes in pigmentation in other skin disorders [ 8 , 9 , 10 ]. These molecules include interleukin-18 (IL-18) and interferon gamma (IFN-γ), among others [ 11 , 12 , 13 , 14 ]. Accordingly, and because the type IV hypersensitivity mechanism that causes post-inflammatory skin depigmentation has been previously suggested to occur in PA [ 2 ], in this study, the levels of inflammatory ( IL-4 , IL-6 , IL-1β , IL-17A , tumor necrosis factor-alpha, and INFγ ) and oxidative stress-related genes (superoxide dismutase 1 and heme oxygenase 1) were quantified in skin biopsies, and their association with PA was evaluated.…”

DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo

“…Melasma is a common, acquired pigmentary disorder characterized by chronic and relapsing hypermelanosis of sun-exposed areas [6]. Its etiopathogenesis is complex and includes diverse networks of cellular interactions between melanocytes, keratinocytes, Langerhans cells, mast cells, extracellular matrices, and cytokines involved in inflammation, production of growth factors, and hormonal stimuli [18, 19]. Environmental stressors such as solar radiation are the most important factors in triggering melasma.…”

“…Thus, further research on the mechanisms of methylation in genes involved in the physiopathogenesis of melasma may provide more insights for specific treatments. Future perspectives will focus on the association of methylation with the activation of inflammatory genes involved in melasma [19]. Likewise, it will be interesting to evaluate other epigenetic mechanisms such as histone modifications and microRNAs in order to better quantify the intensity of cellular DNA damage and its repair using specific drugs.…”

A cream of herbal mixture to improve melasma

“…[1][2][3] The prevalence of melasma is 1% in general population and as high as 50% in high-risk populations. 4 Previous studies have shown that at least four pathogenesis are involved in the development of melasma, that is melanogenesis/melanin, 5 inflammation, [6][7][8][9] vascularization/vascular factor, 10,11 and defective skin barrier. [12][13][14][15] Although melasma is not life-threatening, it greatly impacts the quality of the life of patients.…”