Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions

¹Bldg. 10, Rm. 9S241, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.

|May 19, 2004

Summary

Uteroglobin (UG) protein suppresses allergic airway inflammation by inhibiting prostaglandin D2-induced inflammatory responses. This study reveals UG

Area of Science:

Background:

Uteroglobin (UG) is an anti-inflammatory protein.
UG-knockout mice show exaggerated allergic airway inflammation.
Cyclooxygenase-2 (COX-2) and prostaglandin D2 (PGD2) are elevated in UG-deficient airways.

Purpose of the Study:

To elucidate the mechanism by which UG suppresses allergic airway inflammation.
To investigate the role of prostaglandin D2 (PGD2) receptor (DP) signaling in airway inflammation.
To determine how UG interferes with DP-mediated inflammatory pathways.

Main Methods:

Analysis of COX-2 expression and PGD2 levels in UG-knockout mice.
Treatment with recombinant UG to assess its effects.
Investigation of DP signaling pathways (p38 MAPK, p44/42 MAPK, PKC) and nuclear factor-kappaB (NF-κB) activation.
Assessment of UG's impact on NF-κB activation and COX-2 gene expression.

Main Results:

UG-knockout mice exhibit increased airway COX-2 and PGD2 levels.
Recombinant UG treatment abrogates these inflammatory markers.
DP signaling activates NF-κB and stimulates COX-2 expression in a cell-type-specific manner.
Recombinant UG inhibits DP-mediated NF-κB activation and COX-2 gene expression.

Conclusions:

UG plays a critical role in suppressing allergen-induced airway inflammation.
UG acts by blocking DP-mediated NF-κB activation and subsequent COX-2 expression.
UG represents a novel innate homeostatic mechanism in mammalian airways against allergic responses.

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