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Toxicology Study of Inhalable Soil Dusts from the Paso del Norte Region. Dr. N. Shane Cutler, Ph.D. University of Utah Salt Lake City, UT SCERP grant A-05-06. Soil Dusts.
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Toxicology Study of Inhalable Soil Dusts from the Paso del Norte Region Dr. N. Shane Cutler, Ph.D. University of Utah Salt Lake City, UT SCERP grant A-05-06
Soil Dusts Soil Dusts are collected from arid regions and separated out into an inhalable 2.5 μm diameter fraction. Cells are treated at 40 μg/cm2 • JE-Juarez City Street Dust, Mexico • WM-West Mesa, New Mexico • DD-Tooele Desert Dust, Utah • WTR-Well Test Road, Arizona • UTEP-U. of Texas, El Paso parking lot • MC-Mancos, Colorado • FB-Ft. Bliss, Texas • BA-Burned Artillery Range, New Mexico
Veranth, et al Environ Health Perspectives. 2006 Mar;114(3):341-9
Univariate correlations of soil-derived dust composition variables with the concentration of IL-6 in the cell media at 24 hr. (A) EC1 (R2 = 0.50). (B) OP (R2 = 0.46). (C) Calcium/aluminum (R2 = 0.21). (D) Endotoxin (R2 = 0.43). (E) Iron (R2 = 0.03). (F) Arsenic + selenium + mercury + lead (R2 = 0.01). Veranth, et al Environ Health Perspectives. 2006 Mar;114(3):341-9
The MAP Kinase Pathways Growth Factors, Mitogens, GPCR Stress, Inflammatory Cytokines, Growth Factors, Mitogens, GPCR Stimulus Raf, Mos, Tpl2 MLK3, TAK, DLK MEKK1,4 MLK3,ASK1 MAPKKK Mek1/2 MKK3/6 MKK4/7 MAPKK U0126 Erk1/2 P38 MAPK α/β/γ JNK1/2/3 MAPK p38i JNKi Biological Response Growth, Differentiation Development Inflammation, Apoptosis, Growth, Differentiation
Inhibitors of Map Kinase Pathways Block IL-6 Production in vitro
Inflammatory Dust Induces p38 MAPK phosphorylation in vitro SOIL DUST UTEP JE WM None p38i: - + - + - + - + phosphop38 ► GAPDH► U0126: - + - + - + - + PhosphoERK ► TotalERK ► JNKi: - + - + - + - + phosphoJNK► TotalJNK ►
- - - - Bronchial Alveolar Lavage
Bronchial Alveolar Lavage - - - -
- - - - Basophil Lymphocyte Eosinophil Monocyte Neutrophil Bronchial Alveolar Lavage Lactate Dehydrogenase IL-6 Total Protein
Inhaled poorly Inhaled well
Basophil Lymphocyte Eosinophil Monocyte Neutrophil
Saline Fine JE Coarse JE phospho38 phosphoJNK Total JNK
The MAP Kinase Pathways Growth Factors, Mitogens, GPCR Stress, Inflammatory Cytokines, Growth Factors, Mitogens, GPCR Stimulus Raf, Mos, Tpl2 MLK3, TAK, DLK MEKK1,4 MLK3,ASK1 MAPKKK Mek1/2 MKK3/6 MKK4/7 MAPKK U0126 Erk1/2 P38 MAPK α/β/γ JNK1/2/3 MAPK p38i JNKi Biological Response Growth, Differentiation Development Inflammation, Apoptosis, Growth, Differentiation
Basophil Lymphocyte Eosinophil Monocyte Neutrophil