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.
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.
Havranek
Thomas
T
Division of Neonatology, Children's National Medical Center, Washington, DC 20010, USA.
Aujla
Pawandeep K
PK
Nickola
Tracey J
TJ
Rose
Mary C
MC
Scavo
Louis M
LM
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000201:enzymology / Q000473:pathology*; D018793:Interleukin-13 / Q000008:administration & dosage; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics
D000485:Allergens; D018793:Interleukin-13; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D010047:Ovalbumin; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases