A critical role for Pin1 in allergic pulmonary eosinophilia in rats

Stephane Esnault, Louis A. Rosenthal, Zhong Jian Shen, Julie B. Sedgwick, Renee J. Szakaly, Ronald L. Sorkness, James S. Malter

Research output: Contribution to journalArticle

35 Scopus citations

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. Conclusion: These data suggest that in vivo Pin1 blockade attenuates GM-CSF and IL-5 production and can selectively reduce eosinophilic allergic inflammation. Clinical implications: Eosinophils can be selectively reduced by Pin1 blockade, despite allergen challenge.

Original languageEnglish (US)
Pages (from-to)1082-1088
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number5
DOIs
StatePublished - Nov 1 2007

Keywords

  • Eosinophil
  • apoptosis
  • asthma
  • cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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