Biologicals

Archives of Toxicology

, Volume 87, Issue 10, pp 1841-1850

Induction of Dectin-1 and asthma-associated signal transduction pathways in RAW 264.7 cells by a triple-helical (1, 3)-β-d glucan, curdlan

  • Thomas. G. RandAffiliated withDepartment of Biology, Saint Mary’s University Email author 
  • , C. RobbinsAffiliated withDepartment of Biology, Saint Mary’s University
  • , D. RajaramanAffiliated withDepartment of Biology, Saint Mary’s University
  • , M. SunAffiliated withDepartment of Biology, Saint Mary’s University
  • , J. D. MillerAffiliated withDepartment of Chemistry, Carleton University

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Abstract

People living in damp buildings are typically exposed to spore and mycelial fragments of the fungi that grow on damp building materials. There is experimental evidence that this exposure to triple-helical (1, 3)-β-d glucan and low molecular weight toxins may be associated with non-atopic asthma observed in damp and moldy buildings. However, the mechanisms underlying this response are only partially resolved. Using the pure (1, 3)-β-d glucan, curdlan, and the murine macrophage cell line, RAW 264.7, there were two objectives of this study. The first was to determine whether signal transduction pathways activating asthma-associated cell signaling pathways were stimulated using mouse transduction Pathway Finder® arrays and quantitative real-time (QRT) PCR. The second objective was to evaluate the dose and temporal responses associated with transcriptional changes in asthma-associated cytokines, the signal transduction receptor gene Dectin-1, and various transcription factor genes related to the induction of asthma using customized RT-PCR-based arrays. Compared to controls, the 10−7 M curdlan treatment induced significant changes in gene transcription predominately in the NFkB, TGF-β, p53, JAK/STAT, P13/AKT, phospholipase C, and stress signaling pathways. The 10−8 M curdlan treatment mainly induced NFkB and TGF-β pathways. Compared to controls, curdlan exposures also induced significant dose- and time-dependent changes in the gene translations. We found that that curdlan as a non-allergenic potentiator modulates a network of transduction signaling pathways not only associated with TH-1, TH-2, and TH-3 cell responses including asthma potentiation, but a variety of other cell responses in RAW 264.7 cells. These results help provide mechanistic basis for some of the phenotypic changes associated with asthma that have been observed in in vitro, in vivo, and human studies and open up a hypothesis-building process that could explain the rise of non-atopic asthma associated with fungi.

Keywords

Trichocomaceae Aspergillaceae Molds Damp buildings Triple-helical (1, 3)-β-d glucan Curdlan Dectin-1 RAW264.7 cells Inflammation-associated genes Non-atopic asthma