Tumor Necrosis Factor‐α and Interleukin (IL)‐1β, IL‐6, and IL‐8 Impair In Vitro Migration and Induce Apoptosis of Gingival Fibroblasts and Epithelial Cells, Delaying Wound Healing

Basso, Fernanda Gonçalves; Pansani, Taísa Nogueira; Turrioni, Ana Paula Silveira; Soares, Diana Gabriela; Costa, Carlos Alberto de Souza; Hebling, Josimeri

doi:10.1902/jop.2016.150713

Cited by 65 publications

(41 citation statements)

References 18 publications

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“…This wound healing impairment was determined to be mediated via the JNK pathway and was confirmed using specific JNK inhibitor (SP600125) in human dermal fibroblasts 131 . Additionally, Basso et al, have reported that IL‐1β impaired in vitro migration and delayed wound healing process in gingival epithelial and fibroblasts 132 . Therefore, during inflammation, delayed healing and impaired cell migration are present which may be mitigated by SMM‐189 treatment via enhancement of p‐JNK that would improve overall periodontal health.…”

Section: Discussionmentioning

confidence: 85%

Cannabinoid type‐2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL‐1β stimulated primary human periodontal ligament fibroblasts

Abidi

Alghamdi

Dabbous

et al. 2020

J of Periodontal Research

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Objective The aim of this study is to understand the role of cannabinoid type 2 receptor (CB2R) during periodontal inflammation and to identify anti‐inflammatory agents for the development of drugs to treat periodontitis (PD). Background Cannabinoid type 2 receptor is found in periodontal tissue at sites of inflammation/infection. Our previous study demonstrated anti‐inflammatory responses in human periodontal ligament fibroblasts (hPDLFs) via CB2R ligands. Methods Anandamide (AEA), HU‐308 (agonist), and SMM‐189 (inverse agonist) were tested for effects on IL‐1β‐stimulated cytokines, chemokines, and angiogenic and vascular markers expressed by hPDLFs using Mesoscale Discovery V‐Plex Kits. Signal transduction pathways (p‐c‐Jun, p‐ERK, p‐p‐38, p‐JNK, p‐CREB, and p‐NF‐kB) were investigated using Cisbio HTRF kits. ACTOne and Tango™ ‐BLA functional assays were used to measure cyclic AMP (cAMP) and β‐arrestin activity. Results IL‐1β stimulated hPDLF production of 18/39 analytes, which were downregulated by the CB2R agonist and the inverse agonist. AEA exhibited pro‐inflammatory and anti‐inflammatory effects. IL‐1β increased phosphoproteins within the first hour except p‐JNK. CB2R ligands attenuated p‐p38 and p‐NFĸB, but a late rise in p‐38 was seen with HU‐308. As p‐ERK levels declined, a significant increase in p‐ERK was observed later in the time course by synthetic CB2R ligands. P‐JNK was significantly affected by SMM‐189 only, while p‐CREB was elevated significantly by CB2R ligands at 180 minutes. HU‐308 affected both cAMP and β‐arrestin pathway. SMM‐189 only stimulated cAMP. Conclusion The findings that CB2R agonist and inverse agonist may potentially regulate inflammation suggest that development of CB2R therapeutics could improve on current treatments for PD and other oral inflammatory pathologies.

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Section: Discussionmentioning

confidence: 85%

Cannabinoid type‐2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL‐1β stimulated primary human periodontal ligament fibroblasts

Abidi

Alghamdi

Dabbous

et al. 2020

J of Periodontal Research

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“…A similar effect was observed for TNF‐α, with CM derived from LPADM markedly inhibiting its expression by about 53% (Figure m). Previous studies have shown that elevated levels of proinflammatory cytokines including TNF‐α and IL‐1β can delay wound healing (Basso et al, ). These patterns in gene expression did not completely correspond to the qRT‐PCR results described above likely because the regulation of these two genes is influenced by many factors and culture components.…”

Section: Resultsmentioning

confidence: 99%

Construction of a dermis–fat composite in vivo: Optimizing heterogeneous acellular dermal matrix with in vitro pretreatment

Zhu

Yuan

Huang

et al. 2019

J Tissue Eng Regen Med

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Dermis–fat composite tissues have been widely used in plastic and reconstructive surgery and were previously constructed using hydrogel‐type scaffolds. The constructs can be used for in vitro cosmetic and pharmaceutical testing but are not mechanically strong enough for in vivo applications. In this study, we used heterogeneous (porcine) acellular dermal matrix (PADM) as dermal layer scaffold. PADM was pretreated with the laser micropore technique and then precultured with rat adipose‐derived stem cells (rADSCs) in vitro. rADSCs proliferated well on pretreated/unpretreated PADM, showing increased expression of genes associated with inflammatory regulation, proangiogenesis, and stemness, indicating that pretreated/unpretreated PADM both provide a beneficial microenvironment for rADSCs to exert their paracrine function. After in vitro processing, the rADSCs–polyporous PADM and PADM without pretreatments were implanted into the back of rats respectively, followed by adipose tissue transplantation. After implantation, the inflammation induced by pretreated PADM was significantly attenuated and localized compared to the unpretreated group. Moreover, the vascularization was faster, and more adipose tissue was formed in the pretreated group. Sound dermis–fat composite tissue was constructed with sufficient strength, which can potentially be used for actual repair application.

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“…4). Cell migration is adversely affected by inflammatory cytokines for epithelial cells and gingival fibroblasts (26). In summary, the present results indicate that IL-1β alters colocalizations of laminin 5, plectin, and type IV collagen with β4 integrin.…”

Section: Discussionmentioning

confidence: 50%

IL-1β enhances cell adhesion through laminin 5 and β4 integrin in gingival epithelial cells

et al. 2019

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The junctional epithelium and dental enamel adhere because of hemidesmosomes containing laminin 5 and α6β4 integrin, which are important adhesion molecules in the internal basal lamina. Interleukin (IL)-1 is important in the pathogenesis of periodontal disease. IL-1β induces bone resorption by activating osteoclasts; however, its effects on adhesion of epithelial cells remain to be clarified. Laminin β3, β4 integrin, and focal adhesion kinase mRNA levels were higher after 1 h and 3 h of stimulation with IL-1β (1 ng/mL), and IL-1β, type I α1, and type IV α1 collagen mRNA levels were higher after 1 h and lower after 3 h of stimulation with IL-1β. After IL-1β stimulation, colocalization of laminin 5 and β4 integrin was increased after 1 h, colocalization of β4 integrin and plectin was increased after 1 h and decreased after 3 h, and colocalization of β4 integrin and type IV collagen was decreased after 3 h. Wound healing assays showed that IL-1β treatment (3 h) delayed wound healing. These results suggest that IL-1β enhances cell adhesion by altering localization of epithelial adhesion molecules.

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Tumor Necrosis Factor‐α and Interleukin (IL)‐1β, IL‐6, and IL‐8 Impair In Vitro Migration and Induce Apoptosis of Gingival Fibroblasts and Epithelial Cells, Delaying Wound Healing

Abstract: Demonstrated results indicate negative effects of tested inflammatory cytokines on ECs and GFs, inducing apoptosis and impairing cell migration. These results can justify delayed oral mucosa healing in the presence of inflammatory reaction.

Cited by 65 publications

References 18 publications

Cannabinoid type‐2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL‐1β stimulated primary human periodontal ligament fibroblasts

Cannabinoid type‐2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL‐1β stimulated primary human periodontal ligament fibroblasts

Construction of a dermis–fat composite in vivo: Optimizing heterogeneous acellular dermal matrix with in vitro pretreatment

IL-1β enhances cell adhesion through laminin 5 and β4 integrin in gingival epithelial cells

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