Repeated ultraviolet irradiation induces the expression of Toll‐like receptor 4, <scp>IL</scp>‐6, and <scp>IL</scp>‐10 in neonatal human melanocytes

Song, Hyung Keun; Lee, Si Hyub; Choi, Gwang Seong; Shin, Jeonghyun

doi:10.1111/phpp.12359

Cited by 13 publications

(13 citation statements)

References 26 publications

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“…UVB induces a number of cytokines in different cell types, of which IL-6, IL-8, and CXCL-1 are known to respond in primary melanocytes (Song et al, 2018), and CXCL-10 was first found here. Our findings show that the four mediators induced by UVB were further up-regulated by depolymerization of hyaluronan and that IL8 and CXCL1 responded to melanocyte hyaluronan coat disturbance even in the absence of UVB.…”

Section: Discussionmentioning

confidence: 62%

“…UVR is the main risk factor for skin melanoma (Valejo Coelho et al, 2016). Although UVA (320À400 nm) may be immunosuppressive (Dupont et al, 2013), UVB (280À320 nm) promotes inflammation, apoptosis, the activation of immune cells, and the secretion of various cytokines and chemokines, such as IL-6, IL-10, and IFN-inducible protein 10 (i.e., IP-10/CXCL-10) (Aoki and Moro, 2005;Song et al, 2018). During melanoma progression, the increased secretion of IL-6 and IL-8 supposedly drives cell proliferation and invasion (Lazar-Molnar et al, 2000;Schadendorf et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Takabe

Kärnä

Rauhala

et al. 2019

Journal of Investigative Dermatology

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Skin is constantly exposed to UVR, the most critical risk factor for melanoma development. Hyaluronan is abundant in the epidermal extracellular matrix and may undergo degradation by UVR. It is hypothesized that an intact hyaluronan coat around the cells protects against various agents including UVR, whereas hyaluronan fragments promote inflammation and tumorigenesis. We investigated whether hyaluronan contributes to the UVB-induced inflammatory responses in primary melanocytes. A single dose of UVB suppressed hyaluronan secretion and the expression of hyaluronan synthases HAS2 and HAS3, the hyaluronan receptor CD44, and the hyaluronidase HYAL2, as well as induced the expression of inflammatory mediators IL6, IL8, CXCL1, and CXCL10. Silencing HAS2 and CD44 partly inhibited the inflammatory response, suggesting that hyaluronan coat is involved in the process. UVB alone caused little changes in the coat, but its removal with hyaluronidase during the recovery from UVB exposure dramatically enhanced the surge of these inflammatory mediators via TLR4, p38, and NF-kB. Interestingly, exogenous hyaluronan fragments did not reproduce the inflammatory effects of hyaluronidase. We hypothesize that the hyaluronan coat on melanocytes is a sensor of tissue injury. Combined with UVB exposure, repeated injuries to the hyaluronan coat could maintain a sustained inflammatory state associated with melanomagenesis.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Takabe

Kärnä

Rauhala

et al. 2019

Journal of Investigative Dermatology

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“…TLR4 activation by LPS induces the expression of tyrosinase and its transcription factor MITF in melanocytes via the activation of p38 MAPK (mitogen-activated protein kinase) [51] (Figure 4, Table 1). In human neonatal melanocytes, repeated UV irradiation increases TLR4 expression and pigmentation [93]. LPS stimulation with repeated UV irradiation induces IL-6 secretion from human neonatal melanocytes, suggesting that melanocytes participate in UV-induced immune modulation [93].…”

Section: Tlr4 and Melanocyte Functionsmentioning

confidence: 99%

Melanogenesis Connection with Innate Immunity and Toll-Like Receptors

Koike

Yamasaki

2020

IJMS

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The epidermis is located in the outermost layer of the living body and is the place where external stimuli such as ultraviolet rays and microorganisms first come into contact. Melanocytes and melanin play a wide range of roles such as adsorption of metals, thermoregulation, and protection from foreign enemies by camouflage. Pigmentary disorders are observed in diseases associated with immunodeficiency such as Griscelli syndrome, indicating molecular sharing between immune systems and the machineries of pigment formation. Melanocytes express functional toll-like receptors (TLRs), and innate immune stimulation via TLRs affects melanin synthesis and melanosome transport to modulate skin pigmentation. TLR2 enhances melanogenetic gene expression to augment melanogenesis. In contrast, TLR3 increases melanosome transport to transfer to keratinocytes through Rab27A, the responsible molecule of Griscelli syndrome. TLR4 and TLR9 enhance tyrosinase expression and melanogenesis through p38 MAPK (mitogen-activated protein kinase) and NFκB signaling pathway, respectively. TLR7 suppresses microphthalmia-associated transcription factor (MITF), and MITF reduction leads to melanocyte apoptosis. Accumulating knowledge of the TLRs function of melanocytes has enlightened the link between melanogenesis and innate immune system.

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“…Stimulation of melanocytes with lipopolysaccharide (LPS), a major component of the cell wall of Gram‐negative bacteria, upregulated the expression of TLR4 and MyD88 mRNA, activated the central transcription factor NF‐κB and enhanced the expression of some proinflammatory cytokines and chemokines . It was also found that TLR4 expression in melanocytes was upregulated by repeated low‐dose UVA or UVB irradiation …”

Section: Introductionmentioning

confidence: 99%

“…Several studies suggest a role of TLRs in the modulation of melanogenesis and in microbial‐ or inflammation‐related changes in skin pigmentation. It was demonstrated that the activation of TLR4 increased melanin synthesis in human melanocytes and induced pigmentation of cultured skin . Similarly, the stimulation of TLR2, TLR3 and TLR9 with their agonists enhanced melanogenesis in melanocytes, while activation of TLR5 and TLR7 reduced melanin content of melanocytes and inhibited body pigmentation of zebrafish embryos …”

Section: Introductionmentioning

confidence: 99%

Differential expression of inflammatory cytokines and chemokines in lipopolysaccharide‐stimulated melanocytes from lightly and darkly pigmented skin

Tam

Dzierżęga‐Lęcznar

Stępień

2019

Experimental Dermatology

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Increasing evidence suggests that human epidermal melanocytes play an important role in the skin immune system; however, a role of their pigmentation in immune and inflammatory responses is poorly examined. In the study, the expression of Toll‐like receptor 4 (TLR4) and inflammatory cytokines and chemokines by cultured normal melanocytes derived from lightly and darkly pigmented skin was investigated after cell stimulation with lipopolysaccharide (LPS). The basal TLR4 mRNA level in heavily pigmented cells was higher as compared to their lightly pigmented counterparts. Melanocyte exposure to LPS upregulated the expression of TLR4 mRNA and enhanced the DNA‐binding activity of NF‐κB p50 and p65. We found substantial differences in the LPS‐stimulated expression of numerous genes encoding inflammatory cytokines and chemokines between the cells with various melanin contents. In lightly pigmented melanocytes, the most significantly upregulated genes were nicotinamide phosphoribosyltransferase (NAMPT/visfatin), the chemokines CCL2 and CCL20, and IL6, while the genes for CXCL12, IL‐16 and the chemokine receptor CCR4 were the most significantly upregulated in heavily pigmented cells. Moreover, the lightly pigmented melanocytes secreted much more NAMPT, CCL2 and IL‐6. The results of our study suggest modulatory effect of melanogenesis on the immune properties of normal epidermal melanocytes.

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Repeated ultraviolet irradiation induces the expression of Toll‐like receptor 4, IL‐6, and IL‐10 in neonatal human melanocytes

Abstract: These results suggest that human melanocytes may actively participate in UV-induced immune modulation.

Cited by 13 publications

References 26 publications

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Melanocyte Hyaluronan Coat Fragmentation Enhances the UVB-Induced TLR-4 Receptor Signaling and Expression of Proinflammatory Mediators IL6, IL8, CXCL1, and CXCL10 via NF-κB Activation

Melanogenesis Connection with Innate Immunity and Toll-Like Receptors

Differential expression of inflammatory cytokines and chemokines in lipopolysaccharide‐stimulated melanocytes from lightly and darkly pigmented skin

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