Sequential induction of prostaglandin E and D synthases in inflammation

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Research

Background:

• Prostaglandin D2 (PGD2) and its metabolite 15-deoxy-Delta(12,14)-PGJ2 are implicated in resolving inflammation.
• Understanding the temporal regulation of prostaglandin synthases during inflammation is crucial.

Purpose of the Study:

• To investigate the sequential transcriptional induction of prostaglandin E and D synthases in the mouse heart during systemic inflammation.
• To examine the expression patterns of cyclooxygenase-2 (COX-2), membrane-bound prostaglandin E synthase-1 (m-PGES-1), and hematopoietic prostaglandin D synthase (H-PGDS).

Main Methods:

• Systemic inflammation was induced in mice using endotoxin.
• Quantitative real-time PCR was used to measure mRNA levels of various inflammatory mediators and prostaglandin synthases.
• The expression of peroxisome proliferator-activated receptor gamma (PPARγ) was also assessed.

Main Results:

• Interleukin-1beta (IL-1β) expression peaked at 4 hours and returned to basal levels within 3-5 days.
• COX-2 and m-PGES-1 expression peaked at 4 hours post-endotoxin.
• H-PGDS expression was significantly upregulated at or after 48 hours, while lipocalin-type PGD synthase (L-PGDS) expression remained unchanged.
• PPARγ mRNA levels increased between 4 and 24 hours.
• Inhibition of PGE2 and PGD2 biosynthesis with NSAIDs led to increased IL-1β expression.

Conclusions:

• The findings support a sequential induction of prostaglandin synthases during inflammation, with a later upregulation of H-PGDS.
• This suggests a shift towards PGD2 biosynthesis, potentially contributing to the resolution of inflammation.
• The results highlight the complex interplay between prostaglandin synthesis and inflammatory responses in the heart.