LL-37 alone and in combination with IL17A enhances proinflammatory cytokine expression in parallel with hyaluronan metabolism in human synovial sarcoma cell line SW982-A step toward understanding the development of inflammatory arthritis.
Kuensaen. Chakkrapong C; Chomdej. Siriwadee S; Kongdang. Patiwat P; Sirikaew. Nutnicha N; Jaitham. Rungnaree R; Thonghoi. Supitcha S; Ongchai. Siriwan S
Key Findings
- LL‑37 quickly raises IL‑6 and IL‑17A gene activity in joint‑derived cells
- When LL‑37 and IL‑17A are together they boost inflammatory genes (PTGS2, TNF) and hyaluronan‑related genes, leading to more PGE2, TNF and HA production
- The combo also increases cell invasion and FN1 expression without harming cell survival, and activates IKK/p65 signaling
Practical Outcomes
- For biohackers, the take‑away is that boosting LL‑37 levels might amplify inflammation rather than help health, so any attempts to raise this peptide should be approached with caution. The findings don’t suggest a usable protocol for longevity or performance.
Summary
The study shows that the natural peptide LL‑37 can trigger strong inflammation and changes in joint‑cell behavior, especially when paired with another inflammatory molecule, IL‑17A. This could make arthritis worse, but it doesn’t give any direct tips for health hacks or longevity.
Abstract
LL-37 is the only human cathelicidin-family host defense peptide and has been reported to interact with invading pathogens causing inflammation at various body sites. Recent studies showed high levels of LL-37 in the synovial-lining membrane of patients with rheumatoid arthritis, a common type of inflammatory arthritis. The present study aims to investigate the role of LL-37 on mechanisms associated with pathogenesis of inflammatory arthritis. The effects of LL-37 on the expression of proinflammatory cytokines, hyaluronan (HA) metabolism-related genes, cell death-related pathways, and cell invasion were investigated in SW982, a human synovial sarcoma cell line. Time-course measurements of proinflammatory cytokines and mediators showed that LL-37 significantly induced IL6 and IL17A mRNA levels at early time points (3-6 hr). HA-metabolism-related genes (i.e., HA synthase 2 (HAS2), HAS3, hyaluronidase 1 (HYAL1), HYAL2, and CD44) were co-expressed in parallel. In combination, LL-37 and IL17A significantly enhanced PTGS2, TNF, and HAS3 gene expression concomitantly with the elevation of their respective products, PGE2, TNF, and HA. Cell invasion rates and FN1 gene expression were also significantly enhanced. However, LL-37 alone or combined with IL17A did not affect cell mortality or cell cycle. Treatment of SW982 cells with both LL-37 and IL17A significantly enhanced IKK and p65 phosphorylation. These findings suggest that the chronic production of a high level of LL-37 may synchronize with its downstream proinflammatory cytokines, especially IL17A, contributing to the co-operative enhancement of pathogenesis mechanisms of inflammatory arthritis, such as high production of proinflammatory cytokines and mediators together with the activation of HA-metabolism-associated genes and cell invasion.
Study Information
pubmed
2019
2019-07-01T00:00:00.000Z
10.1371/journal.pone.0218736
9
55