Poly(ADP-ribosyl)ation in asthma and other lung diseases.
Inhibition of poly(ADP-ribosyl)ation in oxidative stress-related pathologies has recently emerged as a very effective anti-inflammatory intervention in animal models of arthritis, colitis, diabetes and shock. Recent data from three laboratories also support the role of poly(ADP-ribose) polymerase-1 (PARP-1) activation in asthma. Similarly to other inflammatory conditions, the protective effects of PARP inhibition and the PARP-1 knock out phenotype in asthma models have been attributed to inhibition of inflammatory signal transduction (mainly via NF-kappaB) and of oxidative stress-induced cell dysfunction and tissue injury. Here I discuss the complex role of poly(ADP-ribosyl)ation in the regulation of inflammatory cell migration, chemokine and cytokine production and expression of other inflammatory mediators (inducible nitric oxide synthase, matrix metalloproteinases) in asthma. The role of PARP-1 in other oxidative stress-related lung diseases such as asbestosis, silicosis, acute respiratory distress syndrome and ischemia-reperfusion injury is also reviewed.
Virág
László
L
Department of Medical Chemistry, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, H-4026 Debrecen, Bem tér 18/B, Hungary. lvirag@dote.hu
D000818:Animals; D017209:Apoptosis; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology*; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006026:Glycoside Hydrolases / Q000502:physiology; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000209:etiology; D015427:Reperfusion Injury / Q000209:etiology; D012128:Respiratory Distress Syndrome / Q000209:etiology
D016207:Cytokines; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase