<i><b>Porphyromonas gingivalis</b></i><b>-induced IL-33 down-regulates hCAP-18/LL-37 production in human gingival epithelial </b><b>cells </b>

Abstract

ABSTRACThCAP-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 3 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.

Vitamin D and Periodontitis: A Systematic Review and Meta-Analysis

“…A possible mechanism for this association whereby vitamin D reduces the risk of periodontitis is through the induction of cathelicidin [ 69 , 70 , 71 , 72 , 73 ]. The vitamin D pathway has been shown to exist in human gingival fibroblasts and periodontal ligaments cells, playing an important role in immune defense in periodontal soft tissues via the activation of the human cationic antimicrobial protein cathelicidin [ 69 , 70 , 71 , 72 ]. Recently, serum 25(OH)D deficiency was associated with decreased hBD−2 and cathelicidin levels in periodontal tissues in gingivitis and chronic periodontitis [ 73 ].…”

A systematic review and critical appraisal of metagenomic and culture studies in hidradenitis suppurativa

“…In addition to work mentioned above, work in periodontal disease has shown that gingival epithelial cells respond to presence of both Prevotella [53,54] and Porphyromonas [55,56] by increasing inflammatory cytokine expression as well as expression of metalloproteinases. [57] These organisms can also neutralize innate immune mechanisms.…”

The multifaceted roles of antimicrobial peptides in oral diseases

“…gingivalis can down-regulate LL37 production (Tada et al, 2017) and directly degrade synthetic LL37 (McCrudden et al, 2013). All of the above limit the role of antimicrobial peptides as a potential therapeutic in the gingival crevice.…”

“…Similarly, LL37 suppressed the P. gingivalis ‐induced proinflammatory responses of human gingival fibroblasts in a paracrine manner (Into et al., 2010). However, P. gingivalis can down‐regulate LL37 production (Tada et al., 2017) and directly degrade synthetic LL37 (McCrudden et al., 2013). All of the above limit the role of antimicrobial peptides as a potential therapeutic in the gingival crevice.…”