A115 ROLE OF GUT SEROTONIN IN ANTIMICROBIAL PEPTIDE PRODUCTION
Bibliographic record
Abstract
Antimicrobial peptides (AMPs) constitute an armory of innate regulators of crucial importance in the gastrointestinal (GI) tract. It is becoming evident that AMPs, especially human β-defensins (hBDs) produced by colonocytes, shape the composition of the microbiota and help maintain gut homeostasis. Defective bacterial clearance and subsequent modulation of gut microbiota, due to abnormal defensin expression, is associated with pathogenesis of various GI diseases including Inflammatory Bowel Disease (IBD). Serotonin or 5-hydroxytrytophan (5-HT) is a neurotransmitter and hormone that contributes to the regulation of various physiological functions in GI tract. Changes in gut 5-HT signaling are observed in IBD as well as in experimental colitis. Enterochromaffin (EC) cells of the human GI tract are the largest producers of 5-HT, and 5-HT biosynthesis depends on the rate-limiting tryptophan hydroxylase 1 (Tph1). We have previously demonstrated Tph1-deficient (Tph1-/-) mice, which have significantly lower gut 5-HT levels, exhibited reduced severity of colitis compared to their wild-type (Tph1+/+) littermates; while replenishing 5-HT led to increased severity of colitis. As EC cells are situated in the epithelial layer and epithelial cells express 5-HT receptors, we hypothesize that 5-HT can influence β-defensin production directly by acting on the adjoining epithelial cells in relation to innate defense in the GI tract. To elucidate the role of 5-HT in β-defensin production from intestinal epithelial cells in the context of regulating innate immune response. We utilized human colonic HT-29 cells to assess the level of hBD expression upon stimulation with 5-HT (10–3, 10–7, 10–11 M). Quantitative PCR (qPCR) and conventional ELISA were performed to measure gene expression and protein levels in culture supernatant, respectively. Additionally, we measured mouse β-defensin levels in colonic tissues of naïve Tph1+/+ and Tph1-/-. 5-HT, in a dose dependent manner, regulates hBD production by HT-29 cells, where higher 5-HT concentrations down-regulated both mRNA and protein levels. Moreover, we observed significantly higher levels of total mBD in the colonic tissues of Tph1-/- compared to Tph1+/+, suggesting an inhibitory role of 5-HT in defensin production. Our results illustrate that 5-HT released from EC cells can modulate hBD production from intestinal epithelial cells. These results exemplify novel information on the interaction between 5-HT and hBD in relation to intestinal innate immune response and corroborate with previous findings of attenuated hBD expression in colonic CD patients. CCC
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".