PMID- 19818335
OWN - NLM
STAT- MEDLINE
DCOM- 20100128
LR  - 20171116
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 183
IP  - 1
DP  - 2010 Jan 5
TI  - Inflammation-associated gene transcription and expression in mouse lungs induced 
      by low molecular weight compounds from fungi from the built environment.
PG  - 113-24
LID - 10.1016/j.cbi.2009.09.023 [doi]
AB  - Few metabolites from fungi found indoors have been tested for inflammatory 
      mediators endpoints in primary cultures of alveolar macrophages or in vivo. In 
      this study, mice were intratracheally instilled with a single dose comprising 
      4x10(-5)moletoxin/kg lung wt dose of either atranone C, brevianamide, 
      cladosporin, mycophenolic acid, neoechinulin A & B, sterigmatocystin or TMC-120A. 
      These toxins are from fungi common on damp building materials. The dose used was 
      comparable to the estimated doses of possible human exposure. Hematoxylin and 
      eosin (H&E) histology and Alcian Blue/Periodic Acid Schiff (AB/PAS) 
      histochemistry were used to evaluate lungs for time course (4h and 12h 
      post-exposure (PE)) inflammatory and toxic changes. Reverse-transcription 
      (RT)-PCR based arrays were also employed to evaluate time course 
      inflammation-associated gene transcription in lung tissues of the different 
      toxins. Immunohistochemistry (IHC) was used to probe MIP-2 and Tnf-alpha protein 
      expression in treatment lungs to determine whether responses correspond with gene 
      transcription data. Both histology and histochemistry revealed that toxin exposed 
      lungs at 12h PE showed evidence of inflammation. H&E revealed that bronchioli 
      were lined with irregularly thickened and sometimes sloughing epithelium and 
      bronchiolar spaces supported infiltration of leukocytes, cellular and mucus-like 
      debris while alveolar spaces supported swollen macrophages and modest amorphous 
      debris accumulations. All toxin-instilled lungs exhibited copious mucus 
      production and alveolar macrophages with red stained cytoplasm on bronchiolar 
      surfaces, especially at 12h PE. Array analysis of 83 inflammation-associated 
      genes extracted from lung tissue demonstrated a number of patterns, compared to 
      controls. 82 genes assayed at 4h PE and 75 genes at 12h PE were significantly 
      altered (p< or =0.05; >or =1.5-fold or < or =-1.5-fold change) in the different 
      treatment animal groups. Expression of transcriptionally regulated genes was 
      confirmed using immunohistochemistry that demonstrated MIP-2 and Tnf-alpha 
      staining in respiratory bronchiolar epithelia, alveolar macrophages and alveolar 
      type II cells. The transcriptional regulation in these genes in the treatment 
      groups suggests that they may serve central roles in the immunomodulation of 
      toxin-induced pro-inflammatory lung responses. Hierarchical cluster analysis 
      revealed significant patterns of gene transcription linking the response of the 
      toxins at equimolar doses in three groups: (1) brevianamide, mycophenolic acid 
      and neoechinulin B, (2) neoechinulin A and sterigmatocystin, and (3) cladosporin, 
      atranone C and TMC-120. The results further confirm the inflammatory nature of 
      metabolites/toxins from such fungi can contribute to the development of 
      non-allergenic respiratory health effects.
FAU - Miller, J D
AU  - Miller JD
AD  - Department of Chemistry, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
FAU - Sun, M
AU  - Sun M
FAU - Gilyan, A
AU  - Gilyan A
FAU - Roy, J
AU  - Roy J
FAU - Rand, T G
AU  - Rand TG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Alkaloids)
RN  - 0 (Benzofurans)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Isocoumarins)
RN  - 0 (Isoquinolines)
RN  - 0 (Mycotoxins)
RN  - 0 (Piperazines)
RN  - 0 (TMC 120A)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 10048-13-2 (Sterigmatocystin)
RN  - 25644-25-1 (neoechinulin)
RN  - 81PR0D5FI4 (cladosporin)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Air Pollution, Indoor/*analysis
MH  - Alkaloids/toxicity
MH  - Animals
MH  - Benzofurans/toxicity
MH  - Chemokine CXCL2/genetics/metabolism
MH  - Cluster Analysis
MH  - Fungi/*chemistry
MH  - Gene Expression Profiling
MH  - Inflammation Mediators/*metabolism
MH  - Isocoumarins/toxicity
MH  - Isoquinolines/toxicity
MH  - Lung/*metabolism/pathology
MH  - Macrophages, Alveolar/metabolism
MH  - Male
MH  - Mice
MH  - Mycophenolic Acid/toxicity
MH  - Mycotoxins/*toxicity
MH  - Piperazines/toxicity
MH  - Sterigmatocystin/toxicity
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2009/10/13 06:00
MHDA- 2010/01/29 06:00
CRDT- 2009/10/13 06:00
PHST- 2009/08/22 00:00 [received]
PHST- 2009/09/29 00:00 [revised]
PHST- 2009/09/29 00:00 [accepted]
PHST- 2009/10/13 06:00 [entrez]
PHST- 2009/10/13 06:00 [pubmed]
PHST- 2010/01/29 06:00 [medline]
AID - S0009-2797(09)00426-8 [pii]
AID - 10.1016/j.cbi.2009.09.023 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2010 Jan 5;183(1):113-24. doi: 10.1016/j.cbi.2009.09.023.