IADR Abstract Archives

Multidrug resistance-associated protein 4-mediated prostaglandin E2-transport in inflamed dental pulp

Objectives: Multidrug resistance associated protein (Mrp) 4 is a membrane transport protein that plays a crucial role in the transmembrane uptake and/or efflux of prostaglandins (PGs), and drugs such as nonsteroidal anti-inflammatory drugs. However, the role of this transporter in pulp inflammation is poorly understood. This study aimed to analyze the mRNA and protein expression of Mrp4 and its involvement in the PGE2 efflux transport in lipopolysaccharide (LPS)-inflamed rat incisor pulp.

Methods: Pulpitis was induced in the upper incisor of Wistar rats by applying LPS for 6-24 h. The level of Mrp4 mRNA expression was determined in the LPS-inflamed and normal pulps by using real-time PCR. The protein expression for Mrp4 was analyzed with double immunofluorescence staining using an anti-Mrp4 antibody and CD31 (an endothelial cell marker). The amount of PGE2 released from inflamed pulp explants, in the presence or absence of dipyridamole (an Mrp4 inhibitor), was assessed by an enzyme-linked immunosorbent assay.

Results: The level of Mrp4 mRNA expression in the inflamed pulps was significantly higher at 6-12 h after the LPS application, compared with that in the normal pulp (P < 0.01 at 6 h and P < 0.05 at 12 h). Double immunofluorescent staining revealed that Mrp4-immunoreactivity was colocalized in CD31-expressing endothelial cells. Moreover, the Mrp4 inhibitor caused a 51.8% decrease in the amount of PGE2 released from the LPS-inflamed pulps (P < 0.01 at 24h).

Conclusions: In the LPS-inflamed pulp, Mrp4 mRNA was upregulated and immunolocalized in endothelial cells. The significant decrease of PGE2-release by the Mrp4 inhibitor suggests that this transporter contributes to the transport of PGE2 in the transmembrane efflux pathway.

Division: IADR/AADR/CADR General Session
Meeting: 2013 IADR/AADR/CADR General Session (Seattle, Washington)
Location: Seattle, Washington
Year: 2013
Final Presentation ID: 928
Abstract Category|Abstract Category(s): Pharmacology/Therapeutics/Toxicology
Authors
  • Ohkura, Naoto  ( Niigata University Graduate School of Medical and Dental Sciences, Niigata, N/A, Japan )
  • Shigetani, Yoshimi  ( Niigata University Graguate School of Medical and Dental Sciences, Niigata, N/A, Japan )
  • Yoshiba, Nagako  ( Niigata University Graduate School of Medical and Dental Sciences, Niigata, N/A, Japan )
  • Yoshiba, Kunihiko  ( Niigata University Graduate School of Medical and Dental Sciences, Niigata, N/A, Japan )
  • Okiji, Takashi  ( Niigata University Graduate School of Medical and Dental Sciences, Niigata, N/A, Japan )
  • SESSION INFORMATION
    Poster Session
    Dental and Oral Therapeutics
    03/21/2013