The preference of tryptophan for membrane interfaces: insights from N-methylation of tryptophans in gramicidin channels. Conclusions Our data support that adequate levels of functional L-kynurenine might contribute to the maintenance of a relative immune privilege in the ocular anterior chamber, thereby contributing to the preservation of corneal allogeneic cells. Microarray analysis gives evidence that the large amino acid transporter 1 (LAT1) transporter protein is responsible for this mechanism. The inhibition of T-cell proliferation might depend on rapid delivery of the tryptophan metabolite, L-kynurenine, to the local corneal environment. Results We found IDO and an associated tryptophan/kynurenine transporter protein exchange mechanism upregulated by inflammatory cytokines in HCECs. The expression of IDO and immunological infiltration of rejected human corneal allografts (n=12) were analyzed by immunohistochemistry. Reversed-phase high pressure liquid chromatography (HPLC), western blot, real time polymerase chain reaction (PCR), and microarray analyses were used. Methods An immunological activation profile was determined in proliferation assays of monocytes from healthy donors. We analyzed the expression levels of IDO in human corneal endothelial cells (HCECs) and downstream tryptophan/kynurenine mechanisms in cell culture. The function of L-kynurenine in the human cornea remains unclear. L-kynurenine is a tryptophan metabolite, which may render activated T-cells apoptotic and therefore might modulate an allogenous transplant reaction. Recently in a mouse model, the overexpression of indoeleamine 2,3 dioxigenase (IDO) was led to an extension in corneal allograft survival. Due to significant rates of rejection, treatment of immunological transplant reactions is of wide interest.
Purpose Penetrating keratoplasty has been the mainstay for the treatment of blindness and is the most common form of tissue transplantation worldwide. Lahdou, Imad Scheuerle, Alexander Höftberger, Romana Aboul-Enein, Fahmy PMID:23012433įunction of the tryptophan metabolite, L-kynurenine, in human corneal endothelial cells Ala mutants of these tryptophans appear monomeric and constitutively bind COP1 in plants, but their responses indicate that monomer formation and COP1 binding are not sufficient for UVR8 function. W285 is essential for UVR8 function in plants, whereas W233 is important but not essential for function, and W337 has a lesser role. Mutation of three tryptophans implicated in UV-B photoreception, W233, W285, and W337, impairs photomorphogenic responses to different extents. However, mutation of three other core tryptophans and four at the dimeric interface has no apparent effect on function in vivo. Three tryptophans in the β-propeller core are important in maintaining structural stability and function of UVR8. Here we report the functions of the UVR8 tryptophans in vivo. However, their roles in UV-B responses in plants, and the functional significance of all 14 UVR8 tryptophans, are not known. Studies in yeast and with purified UVR8 implicate several tryptophan amino acids in UV-B photoreception. UV-B exposure causes rapid conversion of UVR8 from dimer to monomer, accumulation in the nucleus, and interaction with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), which functions with UVR8 in UV-B responses. In Vivo Function of Tryptophans in the Arabidopsis UV-B Photoreceptor UVR8[WĪrabidopsis thaliana UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor specifically for UV-B light that initiates photomorphogenic responses in plants.
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