**2.2 Endogenous ligand/indoles**

Recent studies reported that exposing tissue culture media to UV light enhances the induction of AhR-hydroxylase, an enzymatic activity usually associated with CYP1A1 requiring tryptophan for this response [25]. Many studies showed the ability of UV light to induce CYP1A1 in the skin and liver of rats and mice [26], suggesting that a diffusible AhR-ligand was generated in the skin. Thus, FICZ and other photooxidation products of tryptophan may actually be novel chemical messengers of light [25]. The ability of other endogenous indoles and indole metabolites to bind to the AhR has also been reported [27]. These studies demonstrated that tryptophan and naturally occurring tryptophan metabolites (tryptamine and indole acetic acid) can bind to and activate the AhR and AhR-dependent gene expression in both yeast and mammalian cells in culture. Tryptamine was also shown to be a relatively potent competitive inhibitor of CYP1A1-dependent enzymatic activity, suggesting that it may be a substrate for this enzyme [28]. More recently, it was observed that kyneurinine, additional metabolic breakdown products of tryptophan, could activate the AhR signaling pathway [29]. Because these chemicals are relatively weak ligands and only found at low concentration in cells, they are likely not endogenous activators in normal physiological conditions. However, if cellular concentrations of some tryptophan metabolites (i.e., tryptamine) are significantly elevated to 700 nM, for example, in this case, these ligands could activate the AhR receptor [30]. The solar spectrum is composed of various wavelength radiations having specific effects on skin. UV with the wave length between 295 and 215 nm is responsible for most sunburn and DNA damage. UV with the wavelength 315–400 nm could cause immune suppression. The visible light with the wavelength 400–700 nm was reported to enhance the production of reactive oxygen species and cause damage to macromolecules, whereas infrared induces heat damage and also alters mitochondrial integrity in skin cells, resulting in the generation of reactive oxygen species. All the wavelengths in solar spectrum together contribute to skin aging and wrinkling [27]. These findings can change the way we think about skin aging. UV-B was recently shown to interact with AhR in a reaction involving the formation of a tryptophan-derived photoproduct (FICZ) [26, 29]. In other words, the free amino acid tryptophan in skin cell cytoplasm can act as a chromophore to absorb UV-B energy and the resulting photoproduct activates AhR signaling, suggesting that to achieve effective dermo-protection, AhR must be blocked to neutralize some adverse effects of environmental factors.
