Table 1.
Mechanisms of cytokines in the regulation of melanogenesis.
| Cytokines | Main Source | Cells Used for Experiment | Impact on Melanogenesis | Mechanisms of Melanogenesis | Refs. |
|---|---|---|---|---|---|
| IL-4 | Th-cells | Melanocytes | Inhibition | JAK2-STAT6 signaling pathway is used for downregulating the expression of MITF, TYRP1, TYRP2 | [16] |
| IL-13 | Th2 | γδ T-cell | Inhibition | Suppress tyrosinase and DCT through the JAK2–STAT6 | [107] |
| IL-17 | Epithelial cells, Endothelial cells, Fibroblasts |
Melanocytes, Primary pooled human keratinocytes | Inhibition | TNF and IL-17 simultaneously inhibit melanin formation through PKA and MAPK signaling pathways | [93] |
| IL-33 | Keratinocytes, Fibroblasts | Keratinocytes | Promotion | Activate p38 and PKA pathways and thus promote MITF, TYR, TYRP1, TYRP2 expression | [111,112] |
| IL-18 | Monocytes/Macrophages, Keratinocytes | Melanocytes | Promotion | Increase the activity of tyrosinase and upregulate the expression Of TYRP1 and TYRP2 | [113] |
| IL-1α | Langerhans cells, Melanocytes, keratinocytes | Primary melanocytes and swine skin | Promotion | Melanin deposition is increased when IL-1α is combined with KGF | [114] |
| IL-1β | Monocytes/Macrophages, Keratinocytes | Melanoma cell lines (LB2259-MEL and CP50-MEL) | Inhibition | Through the NF-κB and JNK pathways, it downregulates MITF-M expression | [115] |
| IL-6 | Macrophages, T-cells, Adipocyte | Melanocytes | Inhibition | Tyrosinase activity is declined | [15] |
| PGE2 and PGF2α | Fibroblasts, Keratinocytes | Keratinocytes | Promotion | Activate cAMP-dependent pathway and stimulate melanocyte dendrite formation | [116] |
| INF-γ | T-cells, NK cells, NKT cells | B16F10 | Inhibition | Block melanosomal maturation and upregulate STAT1 phosphorylation | [117,118] |
| TNF | Monocytes, Macrophages, Keratinocytes, Dendritic cells, Th1, Th17 and Th22 | Melanocytes, Primary pooled human keratinocytes |
Promotion | Stimulate PKA and MAPK signaling pathways with combination of IL17, and thus inhibit melanin formation | [93] |
| GM-CSF | Macrophages, Keratinocytes and Th cells | Melanocytes | Promotion | Stimulate MAPK pathway and promote melanocyte proliferation, melanin and synthesis | [119] |
IL-33, interleukin-33; IL-18, interleukin-18; PGE2, prostaglandin E2; PGF2α, prostaglandin F2α; IL-1α, interleukin-1α; GM-CSF, granulocyte-macrophage colony stimulating factor; IL-4, interleukin-4; IL-13, interleukin-13; IL-6, interleukin-6; IL-17, interleukin-17; IL-1β, interleukin-1β; TNF, tumor necrosis factor; IFN-γ, interferons-γ; PKA, protein kinase A; MAPK, mitogen-activated protein kinase; JNK, c-Jun N-terminal kinases; JAK-STAT, Janus kinase-signal transducer and activator of transcription; NF-κβ, nuclear factor kappa-B; TYR, tyrosinase; TRRP1, tyrosinase-related protein-1; TRRP2, tyrosinase-related protein-2; MITF, microphthalmia-associated transcription factor; NK cell, natural killer cell; NKT cell, natural killer T cell; Th, T helper cell.