Porphyromonas gingivalis-induced IL-33 down-regulates hCAP-18/LL-37 production in human gingival epithelial cells.
Tada. Hiroyuki H; Shimizu. Takamitsu T; Matsushita. Kenji K; Takada. Haruhiko H
Key Findings
- P. gingivalis infection reduces LL‑37 production in gingival epithelial cells via IL‑33 up‑regulation.
- A gingipains‑deficient mutant of P. gingivalis does not suppress LL‑37 as much, indicating the role of bacterial enzymes.
- Vitamin D analog OCT can increase LL‑37, but its effect is dampened when cells are infected with P. gingivalis.
Practical Outcomes
- Maintain good oral hygiene to limit P. gingivalis colonization, which may help preserve LL‑37 levels and overall innate immunity. Consider vitamin D or its analogs to support LL‑37 production, but effectiveness may depend on oral health status. Targeting IL‑33 pathways could be a future strategy to boost LL‑37 during gum infections.
Summary
The study shows that the gum‑damaging bacteria Porphyromonas gingivalis can lower the body’s natural antimicrobial peptide LL‑37 in gum cells by boosting a molecule called IL‑33. Vitamin D‑like compounds can raise LL‑37, but the bacteria’s effect can block this boost. Keeping the mouth free of this bacteria may help maintain higher LL‑37 levels, which are linked to better immune defense.
Abstract
hCAP-18/LL-37 is an antimicrobial peptide that is mainly expressed in epithelial cells. Gingival epithelial cells play pivotal roles in antimicrobial defense by expressing hCAP-18/LL-37. Porphyromonas gingivalis is a primary pathogen for chronic periodontitis and produces cysteine proteinase gingipains, which induce proinflammatory cytokines production, leading to enhance inflammatory responses. In contrast, gingipains attenuate immune responses, leading to induce anti-inflammatory responses. In this study, we investigated the ability of gingipains to attenuate P. gingivalis-induced hCAP-18/LL-37 production by human gingival epithelial Ca9-22 cells. The expression of LL-37 mRNA was increased by the infection of Ca9-22 cells with a P. gingivalis gingipains-null mutant KDP136 compared with P. gingivalis wild-type strain ATCC 33277. Interleukin (IL)-33 is involved in the development of chronic inflammatory diseases, and P. gingivalis infection increases IL-33 production by human gingival epithelial cells. P. gingivalis-induced LL-37 mRNA expression was augmented in IL-33 small interfering RNA-transfected Ca9-22 cells. Maxacalcitol (22-oxacalcitriol: OCT) is a biologically active metabolite of vitamin D<sub>3</sub> analog, and OCT increases hCAP-18/LL-37 production by human gingival epithelial cells. The increasing expression of LL-37 mRNA by OCT was down-regulated by infection of the cells with P. gingivalis ATCC 33277 in Ca9-22 cells. Furthermore, P. gingivalis infection induced IL-33 mRNA expression in Ca9-22 cells; therefore, P. gingivalis-induced endogenous IL-33 down-regulated hCAP-18/LL-37 production by the bacterium. These findings suggested that endogenous IL-33 down-regulates the induction of hCAP-18/LL-37 production in human gingival epithelial cells.
Study Information
pubmed
2017
2017-06-01T00:00:00.000Z
10.2220/biomedres.38.167
13
37