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Increased poly(ADP-ribose) polymerase (PARP)-1 expression and activity are associated with inflammation but not goblet cell metaplasia in murine models of allergen-induced airway inflammation.

Abstract
Inflammation plays a key role in lung injury and in the pathogenesis of asthma. Two murine models of allergic airway inflammation-sensitization and challenge to ovalbumin (OVA) and intratracheal exposure to interleukin-13 (IL13)-were used to evaluate the expression of poly(ADP-ribose) polymerase-1 (PARP-1) in allergic airway inflammation. Inflammation is prominent in OVA-induced allergic asthma, but this inflammation is greatly reduced by a PARP-1 inhibitor and almost eliminated when PARP-1 knockout mice are subjected to the OVA model. The present study temporally evaluated PARP-1 protein expression, localization, and activity, as well as inflammation and goblet cell metaplasia (GCM), in murine lungs following a single OVA challenge or IL13 exposure. Following OVA challenge PARP-1 protein expression and activity were greatly increased, being maximal at 3 to 5 days following OVA exposure and beginning to decrease by day 8. These changes correlated with the timing and degree of inflammation and GCM. In contrast, PARP-1 protein or activity did not change following single IL13 exposure, though GCM was manifested without inflammation. This study demonstrates that both PARP-1 protein and activity are increased by allergen-activated inflammatory mediators, excluding IL13, and that PARP-1 increase does not appear necessary for GCM, one of the characteristic markers of allergic airway inflammation in murine models.
AuthorsThomas Havranek, Pawandeep K Aujla, Tracey J Nickola, Mary C Rose, Louis M Scavo
JournalExperimental lung research (Exp Lung Res) Vol. 36 Issue 7 Pg. 381-9 (Sep 2010) ISSN: 1521-0499 [Electronic] England
PMID20715980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Allergens
  • Interleukin-13
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Ovalbumin
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
Topics
  • Allergens (immunology)
  • Animals
  • Asthma (enzymology, immunology, pathology)
  • Disease Models, Animal
  • Goblet Cells (enzymology, pathology)
  • Interleukin-13 (administration & dosage)
  • Lung (enzymology, pathology)
  • Male
  • Metaplasia (enzymology, pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Ovalbumin
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases (biosynthesis, genetics)

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