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.

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Presentation transcript:

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 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 Soil Dusts are collected from arid regions and separated out into an inhalable 2.5 μm diameter fraction. Cells are treated at 40 μg/cm 2

Veranth, et al Environ Health Perspectives 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).

The MAP Kinase Pathways Raf, Mos, Tpl2 Mek1/2 Erk1/2 MKK3/6 P38 MAPK α/β/γ MLK3, TAK, DLK MKK4/7 JNK1/2/3 U0126 p38iJNKi Growth Factors, Mitogens, GPCR Stress, Inflammatory Cytokines, Growth Factors, Mitogens, GPCR Inflammation, Apoptosis, Growth, Differentiation Growth, Differentiation Development Stimulus MAPKKK MAPKK MAPK Biological Response MEKK1,4 MLK3,ASK1

Inhibitors of Map Kinase Pathways Block IL-6 Production in vitro

Inflammatory Dust Induces p38 MAPK phosphorylation in vitro TotalERK ► U0126: phosphop38 ► GAPDH► phosphoJNK► TotalJNK ► SOIL DUST UTEP JE WM None p38i: JNKi: PhosphoERK ►

Tracheal Instillation of Soil Dust

Bronchial Alveolar Lavage

Neutrophil Eosinophil Basophil Lymphocyte Monocyte Lactate Dehydrogenase IL-6 Total Protein

Inhaled poorly Inhaled well

Neutrophil Eosinophil Basophil Lymphocyte Monocyte

phospho38 SalineFine JECoarse JE phosphoJNK Total JNK

The MAP Kinase Pathways Raf, Mos, Tpl2 Mek1/2 Erk1/2 MKK3/6 P38 MAPK α/β/γ MLK3, TAK, DLK MKK4/7 JNK1/2/3 U0126 p38iJNKi Growth Factors, Mitogens, GPCR Stress, Inflammatory Cytokines, Growth Factors, Mitogens, GPCR Inflammation, Apoptosis, Growth, Differentiation Growth, Differentiation Development Stimulus MAPKKK MAPKK MAPK Biological Response MEKK1,4 MLK3,ASK1

Neutrophil Eosinophil Basophil Lymphocyte Monocyte