Irsogladine maleate counters the interleukin‐1β‐induced suppression in gap‐junctional intercellular communication but does not affect the interleukin‐1β‐induced zonula occludens protein‐1 levels in human gingival epithelial cells

Fujita, Tsuyoshi; Ashikaga, Arata; Shiba, Hideki; Kajiya, Mikihito; Kishimoto, A.; Hirata, Reika; Tsunekuni, N.; Hirono, Chikara; Kawaguchi, Hiroyuki; Shiba, Yoshiki; Kurihara, Hidemi

doi:10.1111/j.1600-0765.2007.01000.x

Cited by 13 publications

(9 citation statements)

References 26 publications

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“…We previously reported the effectiveness of IM in HGEC following an A. actinomycetemcomitans challenge. The IM treatment had an inhibitory effect on inflammatory cytokines and on the recovery of gap junction intercellular communication in HGEC stimulated with A. actinomycetemcomitans . The increased levels of IL‐6, IL‐8, matrix metalloproteinase‐3 and intercellular adhesion molecule 1‐1 in A. actinomycetemcomitans ‐stimulated HGEC were down‐regulated with IM via the suppression of MAP kinase (p38 and ERK signaling) .…”

Section: Discussionmentioning

confidence: 96%

Irsogladine maleate inhibits Porphyromonas gingivalis‐mediated expression of toll‐like receptor 2 and interleukin‐8 in human gingival epithelial cells

Savitri

Ouhara

Fujita

et al. 2014

J of Periodontal Research

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Section: Discussionmentioning

confidence: 96%

Irsogladine maleate inhibits Porphyromonas gingivalis‐mediated expression of toll‐like receptor 2 and interleukin‐8 in human gingival epithelial cells

Savitri

Ouhara

Fujita

et al. 2014

J of Periodontal Research

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“…The peculiarity of periodontitis implies that the host inflammatory destructive response against biofilm is itself the main cause of the severe damage of the periodontium. In fact, gingival epithelial cells in response to bacterial challenge up-express pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) [ 148 ], which destroy cell-cell junctions also through the downregulation of E-cadherin, connexin and claudin [ 149 , 150 , 151 ].…”

Section: Lf In Oral Pathologies: Surprising Poor Oral Health Relatmentioning

confidence: 99%

Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis

Rosa

Cutone

Lepanto

et al. 2017

IJMS

280

277

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Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH). Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH. In pregnant women, affected by AI, bLf oral administration decreases IL-6 and increases hematological parameters. This surprising effect is unrelated to iron supplementation by bLf (80 μg instead of 1–2 mg/day), but to its role on IIH. AI is unrelated to the lack of iron, but to iron delocalization: cellular/tissue overload and blood deficiency. BLf cures AI by restoring iron from cells to blood through Fpn up-expression. Indeed, anti-inflammatory activity of oral and intravaginal bLf prevents preterm delivery. Promising bLf treatments can prevent/cure transitory inflammation/anemia/oral pathologies in athletes.

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“…Similar to skin wounds, these connexins were down regulated in migrating keratinocytes in the mucosal wounds [ 38 ]. Connexin expression has also been studied in normal human gingival epithelium, where keratinocytes express C×26 and C×43 [ 39 – 41 ]. However, nothing is known about connexin expression and function in gingival connective tissue cells and during gingival wound healing.…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of Connexin 43 in Human Gingival Wound Healing and Fibroblasts

et al. 2015

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Connexins (C×s) are a family of transmembrane proteins that form hemichannels and gap junctions (GJs) on the cell membranes, and transfer small signaling molecules between the cytoplasm and extracellular space and between connecting cells, respectively. Among C×s, suppressing C×43 expression or function promotes skin wound closure and granulation tissue formation, and may alleviate scarring, but the mechanisms are not well understood. Oral mucosal gingiva is characterized by faster wound closure and scarless wound healing outcome as compared to skin wounds. Therefore, we hypothesized that C×43 function is down regulated during human gingival wound healing, which in fibroblasts promotes expression of genes conducive for fast and scarless wound healing. Cultured gingival fibroblasts expressed C×43 as their major connexin. Immunostaining of unwounded human gingiva showed that C×43 was abundantly present in the epithelium, and in connective tissue formed large C×43 plaques in fibroblasts. At the early stages of wound healing, C×43 was strongly down regulated in wound epithelial cells and fibroblasts, returning to the level of normal tissue by day 60 post-wounding. Blocking of C×43 function by C×43 mimetic peptide Gap27 suppressed GJ-mediated dye transfer, promoted migration, and caused significant changes in the expression of wound healing-associated genes in gingival fibroblasts. In particular, out of 54 genes analyzed, several MMPs and TGF-β1, involved in regulation of inflammation and extracellular matrix (ECM) turnover, and VEGF-A, involved in angiogenesis, were significantly upregulated while pro-fibrotic ECM molecules, including Collagen type I, and cell contractility-related molecules were significantly down regulated. These responses involved MAPK, GSK3α/β and TGF-β signaling pathways, and AP1 and SP1 transcription factors. Thus, suppressed function of C×43 in fibroblasts promotes their migration, and regulates expression of wound healing-associated genes via AP1, SP1, MAPK, GSK3α/β and TGF-β signaling pathways, and may promote fast and scarless wound healing in human gingiva.

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Irsogladine maleate counters the interleukin‐1β‐induced suppression in gap‐junctional intercellular communication but does not affect the interleukin‐1β‐induced zonula occludens protein‐1 levels in human gingival epithelial cells

Cited by 13 publications

References 26 publications

Irsogladine maleate inhibits Porphyromonas gingivalis‐mediated expression of toll‐like receptor 2 and interleukin‐8 in human gingival epithelial cells

Irsogladine maleate inhibits Porphyromonas gingivalis‐mediated expression of toll‐like receptor 2 and interleukin‐8 in human gingival epithelial cells

Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis

Expression and Function of Connexin 43 in Human Gingival Wound Healing and Fibroblasts

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