Table 1.
Production of mediators in the skin after exposure to UVR
| Category of mediators | Molecules affected by UVR | Predominant wavelength of UVR | Phenotypic effects |
|---|---|---|---|
| Hypothalamic hormones (43, 62) | CRH | Stimulated by UVC, UVB, and UVA | 1) Stimulations of POMC production and processing in the pituitary or peripheral organs to produce and release of POMC peptides through action of CRH-R1; 2) direct action on peripheral organs and immune cells via corresponding membrane-bound CRH-R1 and CRH-R2 receptors; and 3) actions on the brain after crossing the blood brain barrier (BBB) in circumventricular organs or when the BBB is disrupted |
| CRH-related peptides (1) | Urocortin 1 | UVB | 1) Stimulation of POMC peptides at the central or peripheral levels; 2) action on peripheral and immune organs/cells via CRH-R1 and CRH-R2 receptors; and 3) actions on the brain after crossing the BBB |
| Pituitary hormones (42, 62, 64) | POMC and derived peptides including ACTH, α-MSH, β-MSH, γ-MSH, and β-endorphin. | Stimulated by UVC, UVB, and by UVA only for β-endorphin | 1) Activation of cortisol/corticosterone production in the adrenal cortex or peripheral organs via the ACTH-MC2 axis; 2) regulation of the skin phenotype, immune system, and other peripheral organs through action on MC or opioid receptors; 3) possible receptor-mediated actions in the brain if crossed the BBB; and 4) ACTH may disrupt circadian rhythm; |
| Opioids (45, 65) | PENK-derived met- and leu-enkephalins | 1) Regulation of immune system and peripheral tissue functions through action on opioid receptors and 2) regulation of brain functions after crossing the BBB | |
| Neuropeptides (46, 50) | CGRP and SP | Predominantly UVB with some effects by UVA | 1) Regulation of skin functions through corresponding membrane-bound receptors and 2) nociceptive effects |
| Cytokines (47, 66) | TNFα, IL-1, IL-4 IL-6, IL-10, TGF-β, and IL-33 | Predominantly UVB with some effects by UVA | 1) TNFα, IL-1, and IL-6 activate the central HPA axis or its equivalents in the periphery with downstream regulation of homeostasis and indirect immunosuppressive effects; 2) IL-4, IL-10, and TGF-β act as direct immunosuppressors; and 3) IL-33 has both pro- and anti-inflammatory functions that are context dependent and protective effect on the cardiovascular system |
| Immune cells (47, 66) | T and B regulatory cells, LC, and DC | Predominantly UVB with some effects by UVA | Circulating immune cells will affect the systemic immune response and function of other organs |
| Antimicrobial peptides (47) | Β-defensins, cathelicidin, and LL-37 | UVB |
Antimicrobial, immunoregulatory activities and regulation of the epidermal barrier |
| Biogenic amines and precursors (58, 67) | L-DOPA and dopamine | L-DOPA production is enhanced by UVB and UVA; dopamine is inhibited in the skin, while enhanced in the brain | 1) Action in the brain when L-DOPA crosses the BBB; 2) pleiotropic actions in the periphery through activation of dopaminergic and adrenergic receptors or supplying catecholamine-producing cells/organs with L-DOPA; and 3) actions as neurotransmitters in the sympathetic (SNS) system |
| Biogenic amines (51, 68) |
Serotonin |
Stimulated by UVB and UVA | 1) Action in the brain after active transport through the BBB and 2) pleiotropic actions in the periphery and on the immune system through activation of membrane-bound serotonin receptors. |
| Steroids (62, 69) | Cortisol, corticosterone, and pregnenolone | UVC and UVB | 1) Glucocorticoids will inhibit local and systemic immune system and other organ functions through action on corresponding nuclear receptors; 2) they will affect brain functions if crossed the BBB; 3) cortisol/corticosterone will inhibit the HPA axis; and 4) pregnenolone will serve as precursor for steroid production |
| Secosteroids (17, 70) | Vitamin D3 with full or short side chain; lumisterol3 and tachysterol3 with full or short side chain | UVB acting on the B-ring of 7DHC or 7DHP (7-dehydropregnenolone) or their hydroxymetabolites | Action on VDR (vitamin D receptor) and alternative nuclear receptors to regulate 1) body calcium metabolism, 2) musculoskeletal systems, and 3) functions of immune and other systems or organs including the skin, neuroendocrine system, gastrointestinal tract (GI), brain, and reproductive system |
| Imidazole derivative (71–73) | cis-UCA (urocanic acid) | UVB | Local and systemic immunosuppressive effects through action on 5-HT2A or other receptors. |
| Tryptophan derivatives (74, 75) | FITC (6-formylindolo[3,2-b]carbazole) and other photoproducts | UVB | Local phenotypic effects action through activation of the AhR (aryl-hydrocarbon receptor) with implications for the systemic immune system |
| Melatonin metabolites (19, 76) | N-Acetyl-N-formyl-5-methoxykynurenamine (AFMK), N1-Acetyl-5-Methoxykynuramine (AMK), and 2-and 4-hydroxymelatonin | UVB and UVA | Cytoprotective activities; receptor candidate is represented by the AhR (77) |
| Membrane lipids (60, 78, 79) | PAF (platelet-activating factor) and PAF-like molecules | UVB | Local and systemic immunoregulatory functions by interactions with the PAF receptor |
| Gases (1, 22) | NO and NO− | UVA | 1) Regulation of local vascular, immune, antimicrobial, and barrier functions and 2) systemic vasodilatory effects |
| DNA (3, 80) | CPD (cyclobutane pyrimidine dimer) and 6–4PP | Predominantly UVB with some effects by UVA | Immunosuppression and stimulation of melanogenesis and local POMC activity |
The table lists hormones, neurohormones/neurotransmitters, and immune signals activated by UVB or/and UVA or biologically active chemicals formed in the integument with predictable local or systemic phenotypic effects. These molecules would target specific receptors or regulatory proteins triggering local or systemic signal transduction pathways in response to different wavelengths of UVR. Citations are in parentheses.