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J Allergy Clin Immunol. 2007 Nov;120(5):1082-8. Epub 2007 Aug 27.

A critical role for Pin1 in allergic pulmonary eosinophilia in rats.

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  • 1Waisman Center for Developmental Disabilities, Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.

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.

Comment in

PMID:
17720236
[PubMed - indexed for MEDLINE]
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