Biochemical and Immunological Characterization of 3HKA; a Novel Anti-inflammatory Biogenic Amine

Tryptophan (Trp) catabolism generates over fifty metabolites, including kynurenines, powerful mediators of immune regulation.  We recently reported that: (i) lymphatic endothelial cells (LEC) and dendritic cells (DCs) secrete a previously unidentified biogenic amine, 3HKA, which derives from a lateral pathway of Trp catabolism (ii) 3HKA exhibits a clear anti-inflammatory profile by inhibiting the STAT1/NF-kB pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines; most notably, IL-6, IL12p70 and TNFa; (iii) in vivo, 3HKA exerts protective effects in the experimental model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring. In a model of nephrotoxic lupus, 3HKA improved proteinuria and serum urea nitrogen, overall ameliorating the immune-mediated glomerulonephritis and renal dysfunction.  Additionally, 3HKA and 30 newly generated 3HKA analogs have been proven effective in decreasing ex vivo inflammation in PBMC samples of Lupus patients.