Plasmin is involved in inflammation via protease-activated receptor-1 activation in human dental pulp

Kamio, Naoto; Hashizume, Hideki; Nakao, Sumi; Matsushima, Kiyoshi; Saito, Hiroshi

doi:10.1016/j.bcp.2008.02.018

Cited by 35 publications

(29 citation statements)

References 42 publications

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“…We previously, reported that pulp tissues predominantly express PAR‐1 [Kamio et al, ]. In the current study, we demonstrated that the PAR‐1 antagonist SCH79797 blocked the ability of KLKB1 to strongly increase intracellular Ca 2+ .…”

Section: Discussionsupporting

confidence: 67%

“…In particular, we previously demonstrated that a PAR‐1‐activating peptide mobilized Ca 2+ . However, activating peptides for PAR‐2, PAR‐3, and PAR‐4 mobilized Ca 2+ weakly, if at all [Kamio et al, ]. Notably, KLKB1 induces gene expression in primary aortic vascular smooth muscle via PAR‐1 [Abdallah et al, ], and kallikreins have been shown to directly activate PAR‐1 in a similar manner as thrombin [Yoon et al, ], which cleaves PAR‐1 between Arg‐41 and Ser‐42 in the exodomain [Vu et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, we demonstrated that the PAR‐1 antagonist SCH79797 blocked the ability of KLKB1 to strongly increase intracellular Ca 2+ . Similarly, SCH79797 has been shown to block the concentration‐dependent increase in intracellular Ca 2+ due to the PAR‐activating peptide SFLLRN [Kamio et al, ]. However, intracellular Ca 2+ peaks at a different level when cells are exposed to KLKB1 or SFLLRN, presumably because PAR‐1 is cleaved at different sites [Kamio et al, ].…”

Section: Discussionmentioning

confidence: 99%

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Kallikrein Promotes Inflammation in Human Dental Pulp Cells Via Protease‐Activated Receptor‐1

Hayama

Kamio

Okabe

et al. 2016

J of Cellular Biochemistry

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Plasma kallikrein (KLKB1), a serine protease, cleaves high-molecular weight kininogen to produce bradykinin, a potent vasodilator and pro-inflammatory peptide. In addition, KLKB1 activates plasminogen and other leukocyte and blood coagulation factors and processes pro-enkephalin, prorenin, and C3. KLKB1 has also been shown to cleave protease-activated receptors in vascular smooth muscle cells to regulate the expression of epidermal growth factor receptor. In this study, we investigated KLKB1-dependent inflammation and activation of protease-activated receptor-1 in human dental pulp cells. These cells responded to KLKB1 stimulation by increasing intracellular Ca(2+) , upregulating cyclooxygenase-2, and secreting prostaglandin E2 . Remarkably, SCH79797, an antagonist of protease-activated receptor-1, blocked these effects. Thus, these data indicate that KLKB1 induces inflammatory reactions in human dental tissues via protease-activated receptor 1. J. Cell. Biochem. 117: 1522-1528, 2016. © 2015 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Kallikrein Promotes Inflammation in Human Dental Pulp Cells Via Protease‐Activated Receptor‐1

Hayama

Kamio

Okabe

et al. 2016

J of Cellular Biochemistry

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“…Similarly, PAR-1 antagonists (SCH 79797 and 203099) depress P -selectin expression and platelet aggregation [385] and VEGF release [386]. SCH 79797 also limits myocardial ischemia/reperfusion injury in rat hearts [387] and offsets plasmin-induced IL-8 expression and PGE2 release [388]. Orally active himbacine-based SCH 530348 shows potent antiplatelet activity [389].…”

Section: Antagonisms Against Tf Signaling-evolving Thrombotic or mentioning

confidence: 99%

Tissue Factor, Blood Coagulation, and Beyond: An Overview

Chu

2011

International Journal of Inflammation

180

184

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Emerging evidence shows a broad spectrum of biological functions of tissue factor (TF). TF classical role in initiating the extrinsic blood coagulation and its direct thrombotic action in close relation to cardiovascular risks have long been established. TF overexpression/hypercoagulability often observed in many clinical conditions certainly expands its role in proinflammation, diabetes, obesity, cardiovascular diseases, angiogenesis, tumor metastasis, wound repairs, embryonic development, cell adhesion/migration, innate immunity, infection, pregnancy loss, and many others. This paper broadly covers seminal observations to discuss TF pathogenic roles in relation to diverse disease development or manifestation. Biochemically, extracellular TF signaling interfaced through protease-activated receptors (PARs) elicits cellular activation and inflammatory responses. TF diverse biological roles are associated with either coagulation-dependent or noncoagulation-mediated actions. Apparently, TF hypercoagulability refuels a coagulation-inflammation-thrombosis circuit in “autocrine” or “paracrine” fashions, which triggers a wide spectrum of pathophysiology. Accordingly, TF suppression, anticoagulation, PAR blockade, or general anti-inflammation offers an array of therapeutical benefits for easing diverse pathological conditions.

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“…uPA is a serine protease and converts plasminogen, which is an inactive progenitor, into plasmin, the fibrinolytic enzyme form (Wun ). Plasmin produced by uPA can activate MMPs and degrade the extracellular matrix to destroy inflammatory tissues in dental pulp (Andreasen et al , Hannas et al , Kamio et al ). Degradation of the extracellular matrix helps immune cells migrate in pathological conditions, such as inflammation, thereby contributing to the regeneration of blood vessels and other tissues through immune and inflammatory responses (Romer et al , Shen et al ).…”

Section: Discussionmentioning

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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Plasmin is involved in inflammation via protease-activated receptor-1 activation in human dental pulp

Cited by 35 publications

References 42 publications

Kallikrein Promotes Inflammation in Human Dental Pulp Cells Via Protease‐Activated Receptor‐1

Kallikrein Promotes Inflammation in Human Dental Pulp Cells Via Protease‐Activated Receptor‐1

Tissue Factor, Blood Coagulation, and Beyond: An Overview

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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