Breast regression protein-39 (BRP-39) promotes dendritic cell maturation in vitro and enhances Th2 inflammation in murine model of asthma

Acta Pharmacol Sin. 2012 Dec;33(12):1525-32. doi: 10.1038/aps.2012.154. Epub 2012 Nov 26.

Abstract

Aim: To determine the roles of breast regression protein-39 (BRP-39) in regulating dendritic cell maturation and in pathology of acute asthma.

Methods: Mouse bone marrow-derived dendritic cells (BMDCs) were prepared, and infected with adenovirus over-expressing BRP-39. Ovalbumin (OVA)-induced murine model of acute asthma was made in female BALB/c mice by sensitizing and challenging with chicken OVA and Imject Alum. The transfected BMDCs were adoptively transferred into OVA-treated mice via intravenous injection. Airway hyperresponsiveness (AHR), inflammation and pulmonary histopathology were characterized.

Results: The expression of BRP-39 mRNA and protein was significantly increased in lung tissues of OVA-treated mice. The BMDCs infected with adenovirus BRP-39 exhibited greater maturation and higher activity in vitro. Adoptive transfer of the cells into OVA-treated mice significantly augmented OVA-induced AHR and eosinophilic inflammation. Meanwhile, BRP-39 further enhanced the production of OVA-induced Th2 cytokines IL-4, IL-5 and IL-13, but significantly attenuated OVA-induced IFN-γ production in bronchoalveolar lavage fluid.

Conclusion: In OVA-induced murine model of acute asthma, BRP-39 is over-expressed in lung tissue and augments Th2 inflammatory response and AHR. BRP-39 promotes dendritic cell maturation in vitro. Therefore, BRP-39 may be a potential therapeutic target of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Adoptive Transfer*
  • Animals
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / therapy*
  • Bronchoalveolar Lavage Fluid / immunology
  • Chitinase-3-Like Protein 1
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Disease Models, Animal
  • Female
  • Genetic Vectors
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics
  • Lung / immunology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Th2 Cells / immunology*

Substances

  • Chil1 protein, mouse
  • Chitinase-3-Like Protein 1
  • Cytokines
  • Glycoproteins
  • Ovalbumin