The melatonin precursor tryptophan, an amino acid essential in the human diet, has been shown to display antioxidant effects.1 FICZ (also known as 6-formylindolo[3,2-b]carbazole) is a photoproduct of tryptophan that is engendered by exposure to UVB.2 This column discusses the beneficial and detrimental influence of FICZ in skin health.
Dr. Leslie S. Baumann
Antioxidant activity
In 2005, Trommer and Neubert devised a skin lipid model system to screen 47 various compounds (drugs, plant extracts, other plant constituents, and polysaccharides) for topical antioxidative activity in response to UV-induced lipid peroxidation. Among the drugs evaluated, they observed that tryptophan exerted antioxidant effects.3
Wound healing potential
A murine study by Bandeira et al. in 2015 revealed that tryptophan-induced mitigation of the inflammatory response and indoleamine 2, 3-dioxygenase expression may have enhanced skin wound healing in mice who were repeatedly stressed.4
Antifibrotic activity
In 2018, Murai et al. endeavored to clarify the role of FICZ in regulating the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in normal human dermal fibroblasts. They found that FICZ assists in imparting UV-mediated antifibrotic effects through the AHR/MEK/ERK signal pathway in normal human dermal fibroblasts and, thus, shows promise as a therapeutic option for scleroderma.5
Cutaneous leishmaniasis
In 2019, Rodrigues et al. conducted a quantitative analysis of the relative expression of 170 genes involved in various biological processes in the skin biopsies from patients with cutaneous leishmaniasis caused by infection with either Leishmania major or L. tropica. They identified tryptophan-2,3-deoxygenase as a restriction factor for the disorder.6
Photosensitizing activity
Park et al. showed that FICZ, a tryptophan photoproduct and endogenous high-affinity aryl hydrocarbon receptor (AhR) agonist, exhibits nanomolar photodynamic activity as a UVA photosensitizer in epidermal keratinocytes and, thus, is possibly operative in human skin.7 Syed and Mukhtar add that FICZ is effective at nanomolar concentrations and that future research may elucidate its applicability against UV-induced adverse effects and inflammatory skin conditions.8
FICZ, oxidative stress, and cancer promotion
FICZ is known to display detrimental, as well as beneficial, influences in skin. The tryptophan photoproduct, comparable to UVB, ligates AhR, generates reactive oxygen species, and strongly photosensitizes for UVA. As Furue et al. note, FICZ upregulates the expression of terminal differentiation molecules (i.e., filaggrin and loricrin via AhR), and its application has been shown to suppress cutaneous inflammation in a psoriasis and dermatitis mouse model.2
In 2016, Reid et al. reported that the protein photodamage brought about by endogenous photosensitizers such as tryptophan tyrosine residues can contribute to the deleterious impact of UVA on human skin.9
In 2018, Tanaka et al. showed that FICZ imparts a cascade of events tantamount in some cases to UVB, as it promoted the synthesis of proinflammatory cytokines such as interleukin (IL)-1 alpha, IL-1 beta, and IL-6 and boosted reactive oxygen species generation in human HaCaT keratinocytes in an AhR-dependent fashion. They concluded that observing FICZ activity contributes to the understanding of how UVB damages organisms.10
That same year, Murai et al. assessed the effects of FICZ on TGF-beta-mediated ACTA2 and collagen I expression in normal human dermal fibroblasts. They determined that it may act as a key chromophore and one approach to mitigating the effects of photoaging may be to downregulate FICZ signaling.11
A year earlier, Brem et al. showed that the combined effect of FICZ and UVA engendered significant protein damage in HaCaT human keratinocytes, with the oxidation yielded from the combination of FICZ and UVA blocking the removal of potentially mutagenic UVB-induced DNA photolesions by nucleotide excision repair. The researchers concluded that the development of FICZ may raise the risk of incurring skin cancer resulting from sun exposure via the promotion of photochemical impairment of the nucleotide excision repair proteome, which in turn inhibits the removal of UVB-induced DNA lesions.12
Conclusion
However, the tryptophan photoproduct FICZ, which results from UVB exposure, presents as a complicated substance, conferring healthy and harmful effects. Much more research is necessary to determine how best to harness and direct the useful activities of tryptophan and FICZ without incurring damaging effects. Nanotechnology may be one useful avenue of investigation for this purpose.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Trommer H et al. J Pharm Pharmacol. 2003 Oct;55(10):1379-88.
2. Furue M et al. G Ital Dermatol Venereol. 2019 Feb;154(1):37-41.
3. Trommer H and Neubert RH. J Pharm Pharm Sci. 2005 Sep 15;8(3):494-506.
4. Bandeira LG et al. PLoS One. 2015 Jun 9:10(6):e0128439.
5. Murai M et al. J Dermatol Sci. 2018 Jul;91(1):97-103.
6. Rodrigues V et al. Front Cell Infect Microbiol. 2019 Oct 4;9:338. eCollection 2019.
7. Park SL et al. J Invest Dermatol. 2015 Jun;135(6):1649-58.
8. Syed DN and Mukhtar H. J Invest Dermatol. 2015 Jun;135(6):1478-81.
9. Reid LO et al. Biochemistry. 2016 Aug 30;55(34):4777-86.
10. Tanaka Y et al. Oxid Med Cell Longev. 2018 Nov 25;2018:9298052.
11. Murai M et al. J Dermatol Sci. 2018 Jan;89(1):19-26.
12. Brem R et al. Sci Rep. 2017 Jun 27;7(1):4310.