Topical Application of Nano-sized Graphene Oxide Cream Ameliorates Acute Skin Inflammation in Mice

We have previously shown that nano-sized graphene oxide (NGO) displays anti-inflammatory activities against natural killer T (NKT) cell-mediated sepsis. To address whether NGO could be applied to treat acute skin inflammation. We developed a conventional skin Cetaphil® cream containing NGO (NGO cream) for topical application to skin lesions and investigated its therapeutic efficacy by employing the tape-stripping-induced acute skin inflammation model. Topical application of NGO cream to the wounded area significantly reduced skin lesions compared with the control cream. Moreover, NGO cream treatment prevented the tape-stripping-elicited infiltration of and IL1β production by skin neutrophils and dendritic cells (DCs). Furthermore, such anti-inflammatory effects of NGO cream were attributed to decreased infiltration of IL12-producing DCs and IFNγ-producing cells (e.g., CD4+ T, CD8+ T, γδ T, NK, and NKT cells) into the skin. In addition, topical NGO cream administration enhanced the expression of suppressive molecules such as FR4 on skin regulatory T cells. Through RNA sequencing analysis, we found that the preventive effect of NGO cream on acute skin inflammation may be correlated with the activation of keratinocytes located in the epidermis. Our results support NGO cream as a therapeutic option to control acute skin inflammation. Either control cream- or NGO cream was applied topically to the tape-stripped dorsal skin of B6 mice. Subsequently, the skin were harvested.

既往研究表明，纳米氧化石墨烯（nano-sized graphene oxide, NGO）可发挥对抗自然杀伤T（natural killer T, NKT）细胞介导脓毒症的抗炎活性。为探究NGO是否可用于治疗急性皮肤炎症，我们开发了一款搭载NGO的传统丝塔芙®乳膏（Cetaphil® cream，NGO乳膏）用于皮肤病灶局部给药，并通过胶带剥离诱导的急性皮肤炎症模型评估其治疗效果。相较于对照乳膏，将NGO乳膏局部涂抹于损伤区域可显著减轻皮肤损伤。此外，NGO乳膏治疗可抑制胶带剥离诱导的皮肤中性粒细胞与树突状细胞（dendritic cells, DCs）浸润及白细胞介素1β（IL1β）的产生。进一步研究发现，NGO乳膏的抗炎效应可归因于分泌白细胞介素12的树突状细胞与分泌干扰素γ（IFNγ）的细胞（如CD4+ T细胞、CD8+ T细胞、γδ T细胞、自然杀伤细胞及NKT细胞）向皮肤组织的浸润减少。此外，局部涂抹NGO乳膏可上调皮肤调节性T细胞上抑制性分子FR4（FR4）的表达。通过RNA测序分析，我们发现NGO乳膏对急性皮肤炎症的预防作用可能与表皮层角质形成细胞的活化相关。本研究结果支持NGO乳膏可作为控制急性皮肤炎症的治疗选择。实验中，我们将对照乳膏或NGO乳膏局部施用于经胶带剥离处理的B6小鼠背部皮肤，随后收取皮肤组织。