Inhibition of allergic inflammation by supplementation with 5-hydroxytryptophan

Abstract

Clinical reports indicate that patients with allergy/asthma commonly have associated symptoms of anxiety/depression. Anxiety/depression can be reduced by 5-hydroxytryptophan (5-HTP) supplementation. However, it is not known whether 5-HTP reduces allergic inflammation. Therefore, we determined whether 5-HTP supplementation reduces allergic inflammation. We also determined whether 5-HTP decreases passage of leukocytes through the endothelial barrier by regulating endothelial cell function. For these studies, C57BL/6 mice were supplemented with 5-HTP, treated with ovalbumin fraction V (OVA), house dust mite (HDM) extract, or IL-4, and examined for allergic lung inflammation and OVA-induced airway responsiveness. To determine whether 5-HTP reduces leukocyte or eosinophil transendothelial migration, endothelial cells were pretreated with 5-HTP, washed and then used in an in vitro transendothelial migration assay under laminar flow. Interestingly, 5-HTP reduced allergic lung inflammation by 70-90% and reduced antigen-induced airway responsiveness without affecting body weight, blood eosinophils, cytokines, or chemokines. 5-HTP reduced allergen-induced transglutaminase 2 (TG2) expression and serotonylation (serotonin conjugation to proteins) in lung endothelial cells. Consistent with the regulation of endothelial serotonylation in vivo, in vitro pretreatment of endothelial cells with 5-HTP reduced TNF-α-induced endothelial cell serotonylation and reduced leukocyte transendothelial migration. Furthermore, eosinophil and leukocyte transendothelial migration was reduced by inhibitors of transglutaminase and by inhibition of endothelial cell serotonin synthesis, suggesting that endothelial cell serotonylation is key for leukocyte transendothelial migration. In summary, 5-HTP supplementation inhibits endothelial serotonylation, leukocyte recruitment, and allergic inflammation. These data identify novel potential targets for intervention in allergy/asthma.

Association between serotonin transporter gene polymorphisms and childhood asthma

“…In contrast to reports that support the role of serotonin in asthma, a negative correlation between plasma serotonin levels and the severity of asthma was reported by Abdala-Valencia et al, who showed that allergic inflammation was inhibited after the administration of 5-hydroxytryptophan, a serotonin precursor, in animal models of asthma [24].…”

Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-induced arthritis

“…In the kynurenine pathway, tryptophan is catalyzed into N-formylkynurenine by indoleamine 2,3 dioxygenase (IDO) and then converts into kynurenine. 5-HTP suppresses inflammatory responses in murine models of asthma and sepsis [ 11 , 12 ]. 5-HTP also inhibits the production of pro-inflammatory mediators in different cell lines [ 9 , 10 , 13 ].…”

“…5-HTP taken orally was shown to suppress allergic lung inflammation even though cytokine levels were not decreased on bronchoalveolar lavage [ 12 ]. In the current study, we also found that 5-HTP did not affect the cytokine levels in the serum and the percentages of IFNγ + CD4 + T cells in the spleen.…”

“…5-HTP was found to suppress the activation of p38 and nuclear factor-κB (NF-κB) in fibroblasts [ 9 ], and decrease the expression of interleukin (IL)-17 in peripheral blood mononuclear cells (PBMCs) [ 10 ]. Moreover, 5-HTP suppresses the production of tumor necrosis factor-α (TNFα) in lipopolysaccharide (LPS)-treated mice [ 11 ] and improves allergic lung inflammation in a murine asthma model [ 12 ]. In addition, 5-HTP and its metabolite 5-methoxytryptophan (5-MTP) decreases the expression of cyclooxygenase-2 (COX-2) in A549 cells and suppresses cancer growth and metastasis in mice [ 13 ].…”

5‐hydroxytryptophan attenuates imiquimod‐induced psoriasiform dermatitis probably through inhibition of IL‐17A production and keratinocyte activation

“…5‐hydroxytryptophan (5(OH)Trp) is a tryptophan metabolite, which can be converted to serotonin (5‐hydroxytryptamine, 5‐HT), melatonin, or niacin. 5(OH)Trp had anti‐inflammatory effects in lipopolysaccharide‐induced sepsis, collagen‐induced arthritis and ovalbumin‐induced asthma in mice . The skin cells have the capability to transform tryptophan to 5(OH)Trp with further metabolism to serotonin, melatonin and other downstream metabolites .…”