Expression of human cathelicidin peptide LL-37 in inflammatory bowel disease.
Kusaka. S S; Nishida. A A; Takahashi. K K; Bamba. S S; Yasui. H H; Kawahara. M M; Inatomi. O O; Sugimoto. M M; Andoh. A A
Key Findings
- LL‑37 mRNA and protein are significantly up‑regulated in inflamed IBD mucosa
- TLR‑3 stimulation with poly(I:C) induces LL‑37 expression in colonic subepithelial myofibroblasts via TRIF, TRAF6, TAK1, MAPK, NF‑κB, and AP‑1 pathways
- Exogenously added LL‑37 suppresses LPS‑induced IL‑6 and IL‑8 production in these gut cells
Practical Outcomes
- The findings hint that enhancing the body’s own LL‑37 could help calm gut inflammation, but the research does not provide a direct supplement or dosage protocol. For now, biohackers might consider established ways to support LL‑37 production, such as maintaining adequate vitamin D levels, good sleep, and a gut‑friendly diet, while awaiting safer, proven methods to target this peptide.
Summary
The study found that the natural antimicrobial peptide LL‑37 is produced at higher levels in the inflamed gut lining of ulcerative colitis and Crohn’s disease patients. In lab experiments, a viral‑mimic molecule (poly I:C) activated TLR‑3, which triggered a cascade (TRIF, TRAF6, TAK1, MAPKs, NF‑κB, AP‑1) that increased LL‑37 production in colonic cells, and the peptide then reduced inflammation caused by bacterial LPS.
Abstract
Cathelicidin peptide LL-37 plays an important role in the early host response against invading pathogens via its broad-spectrum anti-microbial activity. In this study, we investigated LL-37 expression in the inflamed mucosa of inflammatory bowel disease (IBD) patients. Furthermore, the regulatory mechanism of LL-37 induction was investigated in human colonic subepithelial myofibroblasts (SEMFs). LL-37 mRNA expression and protein secretion were analysed using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Intracellular signalling pathways were analysed using immunoblotting and specific small interference RNA (siRNA). The expression of LL-37 mRNA was increased significantly in the inflamed mucosa of ulcerative colitis and Crohn's disease. The Toll-like receptor (TLR)-3 ligand, polyinosinic-polycytidylic acid (poly(I:C), induced LL-37 mRNA expression and stimulated LL-37 secretion in colonic SEMFs. The transfection of siRNAs specific for intracellular signalling proteins [Toll/IL-1R domain-containing adaptor-inducing interferon (IFN) (TRIF), tumour necrosis factor receptor-associated factor (TRAF)6, transforming growth factor β-activated kinase (TAK)1] suppressed the poly(I:C)-induced LL-37 mRNA expression significantly. Poly(I:C)-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and activated nuclear factor kappa B (NF-κB) and activating factor protein (AP)-1. siRNAs specific for NF-κB and c-Jun inhibited poly(I:C)-induced LL-37 mRNA expression. LL-37 suppressed lipopolysaccharide (LPS)-induced interleukin (IL)-6 and IL-8 expression significantly in colonic SEMFs. The expression of LL-37 was up-regulated in the inflamed mucosa of IBD patients. LL-37 was induced by TLR-3 stimulation and exhibited an anti-microbial effect via interaction with lipopolysaccharide (LPS).
Study Information
pubmed
2017
2017-09-28T00:00:00.000Z
10.1111/cei.13047
34
39