Evaluation of the Extrapineal Sources of Melatonin in Patients with Lymphocytic Colitis

Abstract

Melatonin can be synthesized by different cells in the gastrointestinal tract. The aim of this study was to evaluate the expression of melatonin-synthesizing enzymes: arylalkylamine-N-acetyltransferase(AANAT) and N-acetylserotonin methyltransferase (ASMT) in colonic mucosa and urinary 6-sulfatoxymelatonin excretion(aMT6s) in patients with lymphocytic colitis(LC) related to the number of intraepithelial lymphocytes(IEL) and enterochromaffin cells (EC). The study included 32 healthy subjects (HS group) and 36 patients with lymphocytic colitis (LC group). The diagnosis was based on histological and immunohistochemical performances using mouse monoclonal antibodies (chromogranin A –LK 2H10). EC were counted in 10 fields of each bioptate at 40x magnification. The level of mRNA expression of AANAT and ASMT was estimated in colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by photometric method. Significant differences were found in obtained results between HS and LC group: the number of IEL 14.1±3.41 vs. 32.4±5.50 per 100 surface colonocytes (p less than 0.001); the number of EC 32.2±10.1 vs. 70.4±21.2 (p less than 0.001); AANAT -1.32±0.47 vs. 2.32±0.65 (pless than 0.001; ASMT – 1.51±0.59 vs. 2.80±0.92 (p less than 0.001) aMT6s- 13.4±4.87 vs. 19.9±6.29 (p less than 0.001). Moreover, a positive correlation was found between the number of EC and ASMT (p= 0.011) and between EC and aMT6s (p less than 0.001). No correlation occurred between the number of IEL and AANAT p=0.932) and AMST (n=0.536) and aMT6s (p=9.288). These results indicate that the enterochromaffin cells in colonic mucosa are the main extrapineal source of melatonin in patients with lymphocytic colitis.

Serotonin in the Pathogenesis of Lymphocytic Colitis

“…Kwon et al showed that serotonin signaling might influence the intestinal immune response through the modulation of the gut microbiota composition and resulted in increased susceptibility to colitis [ 26 ]. Although enhanced levels of 5-HT were reported in several studies in various colon inflammatory conditions, research in LC patients is scarce [ 10 , 15 ]. Fernández-Banares et al showed that the use of a selective serotonin reuptake inhibitor (SSRI) was associated with the development of microscopic colitis, both collagenous and lymphocytic [ 27 ].…”

“…In our previous work, we observed a higher number of colonic enterochromaffin (EC) cells, a subpopulation of enteroendocrine cells (EECs), in patients with LC compared to healthy subjects [ 10 ]. Similar results were obtained in other clinics and laboratories [ 11 , 12 ].…”