Ketoprofen Inhibits Expression of Inflammatory Mediators in Human Dental Pulp Cells

Choi, Eun Kyoung; Kim, Sun Ho; Kang, In Chol; Jeong, Jong Youn; Koh, Joon; Lee, Bin-Na; Oh, Won Mann; Min, Kyung-San; Hwang, Yun Chan

doi:10.1016/j.joen.2013.02.003

Cited by 18 publications

(16 citation statements)

References 19 publications

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“…Fosfomycin has been reported to modulate cytokine production by inhibiting NFkB activation [52]. ketoprofen, although it was observed only to down-regulate the inhibitor of cytokine signalling SOCS3 in the current study, others have reported that it suppresses production of IL-1b and TNFa in LPS-stimulated human dental pulp cells, and to inhibit phosphorylation of ERK and JNK [53].…”

Section: Discussioncontrasting

confidence: 56%

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Todd

Negm

Reps

et al. 2017

Pharmacological Research

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2Abbreviations: BCA, bicinchoninic acid; CV, coefficient of variation; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBMCs, peripheral blood mononuclear cells; RPPA, reverse phase protein array; SSMD, strictly standardised mean difference; TNFR1, tumour necrosis factor receptor-1; TRAPS, TNF receptor associated periodic syndrome; WT, wild type. 3ABSTRACT: TNF Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disease caused by mutations in TNF Receptor 1 (TNFR1). Current therapies for TRAPS are limited and do not target the pro-inflammatory signalling pathways that are central to the disease mechanism. Our aim was to identify drugs for repurposing as anti-inflammatories based on their ability to down-regulate molecules associated with inflammatory signalling pathways that are activated in TRAPS. This was achieved using rigorously optimised, high through-put cell culture and reverse phase protein microarray systems to screen compounds for their effects on the TRAPS-associated inflammatory signalome. 1360 approved, publically available, pharmacologically active substances were investigated for their effects on 40 signalling molecules associated with pro-inflammatory signalling pathways that are constitutively upregulated in TRAPS. The drugs were screened at four ten-fold concentrations on cell lines expressing both wild-type (WT) TNFR1 and TRAPS-associated C33Y mutant TNFR1, or WT TNFR1 alone; signalling molecule levels were then determined in cell lysates by the reversephase protein microarray. A novel mathematical methodology was developed to rank the compounds for their ability to reduce the expression of signalling molecules in the C33Y-TNFR1 transfectants towards the level seen in the WT-TNFR1 transfectants. Seven high-ranking drugs were selected and tested by RPPA for effects on the same 40 signalling molecules in lysates of peripheral blood mononuclear cells (PBMCs) from C33Y-TRAPS patients compared to PBMCs from normal controls. The fluoroquinolone antibiotic lomefloxacin, as well as others from this class of compounds, showed the most significant effects on multiple pro-inflammatory signalling pathways that are constitutively activated in TRAPS; lomefloxacin dose-dependently significantly reduced expression of 7/40 signalling molecules across the Jak/Stat, MAPK, NF-kB and PI3K/AKT pathways. This study demonstrates the power of signalome screening for identifying candidates for drug repurposing.

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Section: Discussioncontrasting

confidence: 56%

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Todd

Negm

Reps

et al. 2017

Pharmacological Research

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“…Previously, ketoprofen was used to inhibit dental pulp inflammation in a laboratory model (Choi et al . ). Ketoprofen is a nonsteroidal anti‐inflammatory agent that is used on oral lesion such as pharyngitis or inflammation of the mouth in orthodontic therapy (Choi et al .…”

Section: Introductionmentioning

confidence: 97%

“…However, ketoprofen does not have a mineralization‐inducing effect on the dental pulp (Choi et al . ).…”

Section: Introductionmentioning

confidence: 97%

“…Therefore, an ideal pulp-capping agent should suppress inflammation and induce pulp tissue mineralization during treatment for cariously exposed pulps (Komabayashi & Zhu 2010). Previously, ketoprofen was used to inhibit dental pulp inflammation in a laboratory model (Choi et al 2013). Ketoprofen is a nonsteroidal anti-inflammatory agent that is used on oral lesion such as pharyngitis or inflammation of the mouth in orthodontic therapy (Choi et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells

et al. 2016

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“…Oral bacteria can invade pulp tissue, causing infection and inflammation (Goldberg & Hirata ). If the inflammation is not controlled, irreversible pulpitis or pulp necrosis can occur (Choi et al , Farges et al , Jung et al ).…”

Section: Introductionmentioning

confidence: 99%

TLR5 activation induces expression of the pro‐inflammatory mediator Urokinase Plasminogen Activator via NF‐κB and MAPK signalling pathways in human dental pulp cells

Hwang

Kim

et al. 2019

Int Endodontic J

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Aim To explore the involvement of TLR5 in pulp inflammation and to examine the effects of TLR5 activation with its ligand, FlaB protein, on pro‐inflammatory gene expression. Methodology TLR5 expression in dental pulp tissues and human dental pulp cells (hDPCs) were determined by immunohistochemistry, immunocytochemistry, Western blots and RT‐PCR analyses. To examine the role of TLR5, hDPCs were treated with recombinant FlaB protein (500 ng mL−1) to activate the receptor or with a small interfering RNA against TLR5 (si‐TLR5) to downregulate the receptor. After exposure to FlaB, the expression of inflammation‐related proteins was screened using a protein array kit. Western blots or qRT‐PCR analyses were performed to identify changes in the expression of uPA (urokinase plasminogen activator), TIMPs (tissue inhibitor of metalloproteinases), and IL‐6 and to determine their signalling pathways. Statistical analysis was performed using one‐way analysis of variance (anova) with Tukey post hoc test; P < 0.05 was considered statistically significant. Result TLR5 expression was identified in pulp tissues and hDPCs. In the protein array analysis, treatment with FlaB significantly increased uPA expression (P < 0.01) and significantly decreased TIMP1/4 (P < 0.05). FlaB treatment also significantly increased expression of the inflammatory marker IL‐6 (P < 0.01). FlaB treatment increased phosphorylation of the NF‐κB p65 subunit, JNK, p38 and ERK. Chemical inhibitors of NF‐κB (Bay11‐7082), p38 (SB202190) or ERK (U0126) decreased the FlaB induction of uPA expression. Downregulation of TLR5 expression by siRNA decreased the FlaB induction of uPA protein and p65 phosphorylation. Conclusion TLR5 activation with FlaB treatment induced the expression of uPA via the NF‐κB and MAPK signalling pathways. Flagellin‐bearing oral bacteria may cause pulp inflammation through TLR5. The findings provide new clues to control pulpal diseases by targeting TLR5 signalling pathways.

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Ketoprofen Inhibits Expression of Inflammatory Mediators in Human Dental Pulp Cells

Cited by 18 publications

References 19 publications

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells

TLR5 activation induces expression of the pro‐inflammatory mediator Urokinase Plasminogen Activator via NF‐κB and MAPK signalling pathways in human dental pulp cells

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