title: A critical role for Pin1 in allergic pulmonary eosinophilia in rats.
abstract: BACKGROUND
  Infiltration, accumulation, and degranulation of eosinophils in the lung are hallmarks of active allergic asthma. The pulmonary response to inhaled allergen triggers the secretion of eosinophil chemoattractants and antiapoptotic cytokines, including GM-CSF, IL-3, IL-4, IL-5, and eotaxin, among others. We recently showed that in vitro Pin1 regulated eosinophil production of and response to GM-CSF.
  
  
  OBJECTIVE
  We sought to determine the effect of Pin1 inhibition on pulmonary eosinophilia after allergen challenge.
  
  
  METHODS
  The Pin1 inhibitor juglone (5-hydroxy-1,4-naphthoquinone) was administered to allergen-sensitized and allergen-challenged Brown Norway rats. Bronchoalveolar lavage fluid and lungs were assessed for inflammation, cytokine expression, and Pin1 activity.
  
  
  RESULTS
  Juglone-treated rats showed a dramatic reduction (approximately 75%) in bronchoalveolar lavage fluid and pulmonary eosinophilia but no change in lymphocyte, monocyte/macrophage, or neutrophil numbers. GM-CSF and IL-5 expression were also significantly reduced, whereas Pin1-independent cytokines, such as eotaxin or IL-4, as well as housekeeping mRNAs and proteins, including actin, were unaffected by juglone. The eosinophils present in the lung in juglone-treated rats showed significantly greater apoptosis.
  
  
  CONCLUSIONS
  These data suggest that in vivo Pin1 blockade attenuates GM-CSF and IL-5 production and can selectively reduce eosinophilic allergic inflammation.
  
  
  CONCLUSIONS
  Eosinophils can be selectively reduced by Pin1 blockade, despite allergen challenge.
authors.affiliation: Waisman Center for Developmental Disabilities, Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
authors.forename: Stephane
authors.initials: S
authors.lastname: Esnault
authors.forename: Louis A
authors.initials: LA
authors.lastname: Rosenthal
authors.forename: Zhong-Jian
authors.initials: ZJ
authors.lastname: Shen
authors.forename: Julie B
authors.initials: JB
authors.lastname: Sedgwick
authors.forename: Renee J
authors.initials: RJ
authors.lastname: Szakaly
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Sorkness
authors.forename: James S
authors.initials: JS
authors.lastname: Malter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009285:Naphthoquinones / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015848:Interleukin-5; D009285:Naphthoquinones; C414604:PDZD2 protein, rat; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C005134:juglone