Protein Kinase C Synergistically Stimulates Tumor Necrosis Factor-α–Induced Secretion of Urokinase-Type Plasminogen Activator in Human Dental Pulp Cells

Abstract

Plasminogen activator (PA) is the enzyme converting plasminogen to its active form, plasmin, involved in various physiological and pathological phenomena. The conversion is catalyzed by two types of PA, urokinase-type PA (uPA) and tissue-type PA (tPA). When human dental pulp cells were stimulated by the inflammatory cytokine tumor necrosis factor-α (TNF-α), PA activity in the conditioned medium was increased, indicating that TNF-α provoked PA secretion. The TNF-α-induced PA release was significantly enhanced in the presence of phorbol-12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator. The PKC inhibitor Ro31-8220 abolished the effect of PMA on the PA release. The activity of PA secreted from the cells stimulated by TNF-α and PMA was reduced by immunoprecipitation using anti-uPA antibody. PMA failed to enhance the TNF-α-induced expression of uPA mRNA. These results suggest that protein kinase C synergistically enhances the secretion of uPA in TNF-α-stimulated human dental pulp cells.

Suppression of PKC-α attenuates TNF-α-evoked cerebral barrier breakdown via regulations of MMP-2 and plasminogen–plasmin system

“…Considering that TNF-α-mediated increases in human dental pulp and umbilical vein endothelial cell uPA levels were regulated by PKC [19,47], we investigated the specific correlation between HBMEC uPA activity and two different PKC isoforms known to have profound relevance to BBB integrity i.e. PKC-α and PKC- Although inhibition of both isoforms significantly mitigated uPA activity, the magnitude of decreases appeared to be grater with PKC-α inhibition.…”

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

“…Various inflammatory mediators, such as TNF‐α, IL‐1β, IL‐6, IL‐8, uPA, and matrix metalloproteinases (MMPs) are released from the suppurative pulpitis and necrotic pulp tissue caused by an oral bacterial infection and regulate biological responses and tissue remodelling (Morand et al , Farges et al ). Amongst them, uPA and MMPs play important roles in tissue remodelling and are not only regulated by bacterial infection but also inflammatory cytokines, such as TNF‐α, IL‐1β (Kamio et al , Hashizume et al , Lin et al ). In this study, TLR5 activation by FlaB treatment increased uPA expression and decreased tissue inhibitors of metalloproteinase (TIMP1/4) expression in hDPCs (Fig.…”