Preferential stimulation of melanocytes by M2 macrophages to produce melanin through vascular endothelial growth factor

Abstract

Post-inflammatory hyperpigmentation is a skin discoloration process that occurs following an inflammatory response or wound. As the skin begins to heal, macrophages first exhibit a proinflammatory phenotype (M1) during the early stages of tissue repair and then transition to a pro-healing, anti-inflammatory phenotype (M2) in later stages. During this process, M1 macrophages remove invading bacteria and M2 macrophages remodel surrounding tissue; however, the relationship between macrophages and pigmentation is unclear. In this study, we examined the effect of macrophages on melanin pigmentation using human induced pluripotent stem cells. Functional melanocytes were differentiated from human induced pluripotent stem cells and named as hiMels. The generated hiMels were then individually cocultured with M1 and M2 macrophages. Melanin synthesis decreased in hiMels cocultured with M1 macrophages but significantly increased in hiMels cocultured with M2 macrophages. Moreover, the expression of vascular endothelial growth factor was increased in M2 cocultured media. Our findings suggest that M2 macrophages, and not M1 macrophages, induce hyperpigmentation in scarred areas of the skin during tissue repair.

Anti-chondrogenic role of nerve growth factor in osteoarthritis and human induced pluripotent stem cells-derived chondrogenesis model

“…hiPSCs culture was performed as described previously (22)(23)(24). Cells were maintained in Essential 8 (E8) medium (Thermo Fisher Scienti c, Waltham, MA, USA) on vitronectin-coated dishes (Thermo Fisher Scienti c), and attached cells were maintained at 37°C in 5% CO 2 .…”

Impaired Osteogenesis in Human Induced Pluripotent Stem Cells with Acetaldehyde Dehydrogenase 2 Mutations

“…ALDH2*1/*1-and ALDH2*1/*2-hiPSCs were generated from peripheral blood mononuclear cells (PBMCs) using a previously described reprogramming method, which involved serial centrifugation and Sendai viruses (Fig. 1A) (12,13). The cells were cultured in vitro nectin-coated dishes (Thermo Fisher Scientific).…”

Dimethyl Itaconate Reduces α-MSH-Induced Pigmentation via Modulation of AKT and p38 MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells

“…Tyrosinase (TYR) functions as a rate-limiting enzyme in melanin production [38]. Oxidation of L-DOPA by intracellular cell lysate is frequently used to estimate TYR activity [39][40][41][42]. However, the studies by Schallreuter et al [43], Land et al [44], and Plonka et al [45] reported that tyrosinases require L-DOPA for their own activation and may not produce dopaquinone via DOPA.…”

“…L-DOPA oxidation was measured as previously described methods with slight modifications [39][40][41][42]. B16F10 cells (5 × 10 4 cells) were seeded at 2 mL per well in two 6-well plates and incubated at 37 • C and 5% CO 2 for 18 h. The cells were then treated with α-MSH (200 nM) alone or with three different concentrations (20,40, and 80 µM) of ITA or DMI and further incubated for 72 h at 37 • C and 5% CO 2 .…”