The combination of sucrose dilaurate and sucrose laurate suppresses HMGB1: an enhancer of melanocyte dendricity and melanosome transfer to keratinocytes

Abstract

BackgroundHyperpigmented spots are common issues in all ethnicities, involving multiple intrinsic and extrinsic factors such as UVB exposure, hormone balance, inflammatory status and ageing.ObjectivesTo determine (i) melanocyte dendricity in multiple facial spot types, (ii) impact of High Mobility Group Box 1 (HMGB1), and the combination of sucrose dilaurate and sucrose laurate (SDL) on melanogenesis and melanocyte dendricity, and (iii) SDL effect on facial spots in a human use test.MethodsFacial spot and adjacent non‐spot skin biopsies were collected from Chinese women (age 20‐70). Histological assessment of melanocyte dendricity was performed for 3 spot types (solar lentigo, melasma and postinflammatory hyperpigmentation) by immunofluorescent staining for c‐kit/MITF. Keratinocyte, melanocyte and melanocyte–keratinocyte co‐culture models were used to assess HMGB1 release by UVB radiation, the effects of HMGB1 and SDL on melanin production, melanocyte dendricity and melanosome transfer. The effect of an SDL‐containing moisturizer on appearance of facial hyperpigmented spots was assessed against a vehicle control in an 8‐week human use test.ResultsMelanocytes in spot areas are more dendritic than melanocytes in adjacent non‐spot skin across three investigated spot types. In cell culture models, a moderate UVB‐radiation exposure caused release of HMGB1 from keratinocytes. HMGB1 did not alter melanin production in melanocytes, but enhanced melanocyte dendricity and melanosome transfer. SDL reduced HMGB1 release from keratinocytes, inhibited melanin production, reversibly suppressed melanocyte dendricity and reduced melanosome transfer. In the human use test, SDL‐containing moisturizer reduced appearance of spots versus vehicle.ConclusionIncreased melanocyte dendricity was observed in multiple types of facial spots. Addition of HMGB1 protein increased melanocyte dendricity and melanosome transfer in cell cultures, implicating potential involvement in spot formation. SDL suppressed melanin production, melanocyte dendricity and melanosome transfer in vitro and reduced appearance of spots in the use test, suggesting SDL is an effective solution to address hyperpigmented spot concerns.

A longitudinal comparative study by in vivo harmonic generation microscopy: Q‐switched ruby laser versus picosecond 532‐nm Nd: YAG laser for the treatment of solar lentigines

“…Increased melanocyte dendricity has been demonstrated by double immunostaining of c-kit and MITF in SLs, melasma and acne-induced PIH. 29 Consistent with the findings, we previously successfully demonstrated that melanocyte dendricity was significantly higher in melasma than that in the surrounding normal skin by in vivo HGM imaging. 30 However, the EMDS of SLs was not higher than the perilesional normal skin in our study which is consistent with the in vivo reflectance confocal microscopy (RCM) study performed by Richtig et al 31 The reason may be due to the high background signals from melanin enhancement in basal keratinocytes of SLs, which interferes with the observation of mild elongation of melanocytic dendrites.…”

“…Increased melanocyte dendricity has been demonstrated by double immunostaining of c‐kit and MITF in SLs, melasma and acne‐induced PIH 29 . Consistent with the findings, we previously successfully demonstrated that melanocyte dendricity was significantly higher in melasma than that in the surrounding normal skin by in vivo HGM imaging 30 .…”

Role of interleukin‐6 and endothelin‐1 receptors in enhanced melanocyte dendricity of facial spots and suppression of their ligands by niacinamide and tranexamic acid

“…With the discovery of (a) enhanced melanocyte dendricity in multiple types of spots; (b) the connection between mediators released in response to UVB damage that enhance melanocyte dendricity; and (c) the heightened sensitivity of spot areas to these mediators due to higher receptor levels, we are conceiving a model in which hyperpigmentation is partially dependent on the hypersensitivity of spot areas to cytokines, leading to an expansion of the distribution network (in length and number) of melanocyte dendrites. The higher dendrite length and number, the higher flux of melanosome distribution and the higher amounts of melanin in a spot area of skin 5 . We have tested the ligands of identified receptors, ET‐1 and IL‐6, in modulating melanocyte dendricity in human melanocyte culture, and demonstrated they can indeed increase melanocyte dendricity in a dose response manner (Figure 3) and enhance melanosome transfer in melanocyte‐keratinocyte co‐culture (Figure 4).…”

“…reported that keratinocyte cultured medium can stimulate melanocyte dendricity; however, of the several known keratinocyte‐derived factors, none could be implicated as a mediator of the observed effects, which include basic fibroblast growth factor, interleukin‐1 alpha, interleukin‐1 beta, 12‐hydroxyeicosatetraenoic acid, prostaglandin E2, leukotriene B4, and adenosine 3′,5′‐cyclic monophosphate analogues. Since then, various keratinocyte‐derived cytokines were discovered to increase melanocyte dendricity, such as nerve growth factor, 10 ET‐1, 11 stem cell factor, 12 alpha‐MSH, 13 secretory phospholipase A2 14 and HMGB1 5 …”

Current Understanding of the Role of Senescent Melanocytes in Skin Ageing

“…For example, H 2 O 2 -treated melanocytes showed nuclear to cytoplasmic translocation and subsequent extracellular release of HMGB1 [ 102 ]. HMGB1 can also be released from keratinocytes upon UV stimulation, acting as a DNA damage ‘warning signal’, and upregulating melanosome transfer and melanocyte dendricity [ 103 ].…”