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Toluene diisocyanat...
Toluene diisocyanate exposure and autotaxin–lysophosphatidic acid signalling
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- Broström, Julia M. (author)
- Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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- Ghalali, Aram (author)
- Karolinska Institute
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- Zheng, Huiyuan (author)
- Karolinska Institutet,Karolinska Institute
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- Högberg, Johan (author)
- Karolinska Institutet,Karolinska Institute
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- Stenius, Ulla (author)
- Karolinska Institutet,Karolinska Institute
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- Littorin, Margareta (author)
- Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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- Tinnerberg, Håkan (author)
- Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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- Broberg, Karin (author)
- Karolinska Institutet,Karolinska Institute,Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English 9 s.
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In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 355, s. 43-51
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Abstract
Subject headings
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- Toluene diisocyanate (TDI) is a reactive chemical used in manufacturing plastics. TDI exposure adversely affects workers' health, causing occupational asthma, but individuals differ in susceptibility. We recently suggested a role for signalling mediated by the enzyme autotaxin (ATX) and its product, lysophosphatidic acid (LPA), in TDI toxicity. Here we genotyped 118 TDI-exposed workers for six single-nucleotide polymorphisms (SNPs) in genes encoding proteins implicated in ATX–LPA signalling: purinergic receptor P2X7 (P2RX7), C–C motif chemokine ligand 2 (CCL2), interleukin 1β (IL1B), and caveolin 1 (CAV1). Two P2RX7 SNPs (rs208294 and rs2230911) significantly modified the associations between a biomarker of TDI exposure (urinary 2,4-toluene diamine) and plasma LPA; two IL1B SNPs (rs16944 and rs1143634) did not. CAV1 rs3807989 modified the associations, but the effect was not statistically significant (p = 0.05–0.09). In vitro, TDI-exposed bronchial epithelial cells (16HBE14o-) rapidly released ATX and IL-1β. P2X7 inhibitors attenuated both responses, but confocal microscopy showed non-overlapping localizations of ATX and IL-1β, and down-regulation of CAV1 inhibited the ATX response but not the IL-1β response. This study indicates that P2X7 is pivotal for TDI-induced ATX–LPA signalling, which was modified by genetic variation in P2RX7. Furthermore, our data suggest that the TDI-induced ATX and IL-1β responses occur independently.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Keyword
- Autotaxin
- Genetic Susceptibility
- Interleukin 1β
- Isocyanate
- Lysophosphatidic Acid
- Purinergic Receptors
- Respiratory Sensitizer
- Toluene Diisocyanate
Publication and Content Type
- art (subject category)
- ref (subject category)
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