Diversified Stimuli-Induced Inflammatory Pathways Cause Skin Pigmentation

Abstract

The production of melanin pigments by melanocytes and their quantity, quality, and distribution play a decisive role in determining human skin, eye, and hair color, and protect the skin from adverse effects of ultraviolet radiation (UVR) and oxidative stress from various environmental pollutants. Melanocytes reside in the basal layer of the interfollicular epidermis and are compensated by melanocyte stem cells in the follicular bulge area. Various stimuli such as eczema, microbial infection, ultraviolet light exposure, mechanical injury, and aging provoke skin inflammation. These acute or chronic inflammatory responses cause inflammatory cytokine production from epidermal keratinocytes as well as dermal fibroblasts and other cells, which in turn stimulate melanocytes, often resulting in skin pigmentation. It is confirmed by some recent studies that several interleukins (ILs) and other inflammatory mediators modulate the proliferation and differentiation of human epidermal melanocytes and also promote or inhibit expression of melanogenesis-related gene expression directly or indirectly, thereby participating in regulation of skin pigmentation. Understanding of mechanisms of skin pigmentation due to inflammation helps to elucidate the relationship between inflammation and skin pigmentation regulation and can guide development of new therapeutic pathways for treating pigmented dermatosis. This review covers the mechanistic aspects of skin pigmentation caused by inflammation.

A Focused review on the pathophysiology of post‐inflammatory hyperpigmentation

“…(Gilchrest et al, 1981) These keratinocyte‐derived factors bind to their specific receptors, located on the melanocyte cell membrane, and activate various signaling pathways, such as the cyclic AMP/protein kinase A pathway, which are involved in the proliferation and differentiation of melanoblasts into melanocytes. (Hossain et al, 2021) Keratinocytes also modulate melanogenesis following ultraviolet (UV) irradiation. (Cichorek et al, 2013) It has been shown that keratinocytes release various inflammatory cytokines including interleukins (IL)‐18, IL‐33, and granulocyte‐monocyte colony stimulating factor (GM‐CSF).…”

“…(Cichorek et al, 2013) To prevent excess production of melanin, these same cytokines, via a negative feedback loop, regulate UV induced melanogenesis and inhibit melanogenesis by downregulating tyrosinase gene expression via activation of NF‐KB. (Hossain et al, 2021)…”

“…Although the role of the dermal compartment in pigmentation has been less extensively studied, there is increasing evidence supporting the role of mesenchymal cells (e.g., fibroblasts) in melanin production. (Hossain et al, 2021; Kapoor et al, 2020) Fibroblasts represent a heterogeneous group of mesenchymal cells that have been shown to influence skin pigmentation by secreting various growth factors including KGF, SCF, and basic fibroblast growth factor. (Hossain et al, 2021) Recent studies have demonstrated the role of growth factors in the pathogenesis of melasma and solar lentigines (SL).…”

“…(Cichorek et al, 2013) To prevent excess production of melanin, these same cytokines, via a negative feedback loop, regulate UV induced melanogenesis and inhibit melanogenesis by downregulating tyrosinase gene expression via activation of NF-KB. (Hossain et al, 2021) In addition to UV light-induced melanogenesis, Randhawa et al (Haass & Herlyn, 2005) used an ex vivo model to elucidate the pigmentation mechanism of VL. It was shown that repeat exposure to VL resulted in de-novo formation of melanin, which appeared to be mediated through an increase in tyrosinase activity.…”

Bioprinting Technology in Skin, Heart, Pancreas and Cartilage Tissues: Progress and Challenges in Clinical Practice

“…Melanocytes reside in the basal layer of the epidermis and they shield skin surface from UV radiation through melanin production, thus playing an important protective role [30]. Some authors tried to produce skin models including also this cell type, with different outcomes [31][32][33] (Table 1).…”