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Bleomycin increases neutrophil adhesion to human vascular endothelial cells independently of upregulation of ICAM-1 and E-selectin (2016)
Journal Article
Williamson, J. D., Sadofsky, L. R., Crooks, M. G., Greenman, J., & Hart, S. P. (2016). Bleomycin increases neutrophil adhesion to human vascular endothelial cells independently of upregulation of ICAM-1 and E-selectin. Experimental Lung Research, 42(8-10), 397-407. https://doi.org/10.1080/01902148.2016.1243742

© 2016 Taylor & Francis. Aim of the Study: Bleomycin-induced lung disease is a serious complication of therapy characterized by alveolar injury, cytokine release, inflammatory cell recruitment, and eventually pulmonary fibrosis. The mechanisms unde... Read More about Bleomycin increases neutrophil adhesion to human vascular endothelial cells independently of upregulation of ICAM-1 and E-selectin.

TRPA1 mediates aromatase inhibitor-evoked pain by the aromatase substrate androstenedione (2016)
Journal Article
Morice, A. H., Sadofsky, L. R., Benemei, S., Coppi, E., De Logu, F., Di Tommaso, M., …Tonello, R. (2016). TRPA1 mediates aromatase inhibitor-evoked pain by the aromatase substrate androstenedione. Cancer Research, 76(23), 7024-7035. https://doi.org/10.1158/0008-5472.CAN-16-1492

Aromatase inhibitors (AI) induce painful musculoskeletal symptoms (AIMSS), which are dependent upon the pain transducing receptor TRPA1. However, as the AI concentrations required to engage TRPA1 in mice are higher than those found in the plasma of p... Read More about TRPA1 mediates aromatase inhibitor-evoked pain by the aromatase substrate androstenedione.

How does rhinovirus cause the common cold cough? (2016)
Journal Article
Atkinson, S. K., Sadofsky, L. R., & Morice, A. H. (2016). How does rhinovirus cause the common cold cough?. BMJ Open Respiratory Research, 3(1), Article e000118. https://doi.org/10.1136/bmjresp-2015-000118

© 2016, BMJ Publishing Group. All rights reserved. Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and has no benefit to the... Read More about How does rhinovirus cause the common cold cough?.

Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable' (2015)
Journal Article
Morgan, K., Sadofsky, L. R., & Morice, A. H. (2015). Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable'. Bioscience Reports, 35(5), Article e00255. https://doi.org/10.1042/BSR20150108

© 2015 Authors. Multiple mis-sense variants of TRPA1 (transient receptor potential A1) and TRPM8 (transient receptor potential M8) are recorded in the human genome single nt polymorphism (SNP) database, but their potential impact on channel signallin... Read More about Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable'.

Human TRPM8 and TRPA1 pain channels, including a gene variant with increased sensitivity to agonists (TRPA1 R797T), exhibit differential regulation by SRC-tyrosine kinase inhibitor (2014)
Journal Article
Morgan, K., Sadofsky, L. R., Crow, C., & Morice, A. H. (2014). Human TRPM8 and TRPA1 pain channels, including a gene variant with increased sensitivity to agonists (TRPA1 R797T), exhibit differential regulation by SRC-tyrosine kinase inhibitor. Bioscience Reports, 34(4), 469-478. https://doi.org/10.1042/BSR20140061

TRPM8 (transient receptor potential M8) and TRPA1 (transient receptor potential A1) are cold-temperature-sensitive nociceptors expressed in sensory neurons but their behaviour in neuronal cells is poorly understood. Therefore DNA expression construct... Read More about Human TRPM8 and TRPA1 pain channels, including a gene variant with increased sensitivity to agonists (TRPA1 R797T), exhibit differential regulation by SRC-tyrosine kinase inhibitor.

Unique responses are observed in transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1) co-expressing cells (2014)
Journal Article
Sadofsky, L. R., Sreekrishna, K. T., Lin, Y., Schinaman, R., Gorka, K., Mantri, Y., …Morice, A. H. (2014). Unique responses are observed in transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1) co-expressing cells. Cells, 3(2), 616-626. https://doi.org/10.3390/cells3020616

Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are implicated in modulation of cough and nociception. In vivo, TRPA1 and TRPV1 are often co-expressed in neurons and TRPA1V1 hetero-tetramer formation is noted in... Read More about Unique responses are observed in transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1) co-expressing cells.

Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts (2012)
Journal Article
Sadofsky, L. R., Ramachandran, R., Crow, C., Cowen, M., Compton, S. J., & Morice, A. H. (2012). Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts. Experimental Lung Research, 38(2), 75-81. https://doi.org/10.3109/01902148.2011.644027

Lung fibroblasts are involved in interstitial lung disease, chronic asthma, and chronic obstructive pulmonary disease (COPD). The expanded fibroblast population in airway disease leads to airway remodeling and contributes to the inflammatory process... Read More about Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts.

The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system (2011)
Journal Article
Nassini, R., Materazzi, S., Vriens, J., Prenen, J., Benemei, S., De Siena, G., …Geppetti, P. (2012). The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system. Brain, 135(2), 376-390. https://doi.org/10.1093/brain/awr272

The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating proper... Read More about The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system.

Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis (2011)
Journal Article
Botham, A., Guo, X., Xiao, Y. P., Morice, A. H., Compton, S., & Sadofsky, L. R. (2011). Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis. Biochemical Journal, 438(2), 359-367. https://doi.org/10.1042/BJ20101958

hPAR2 (human proteinase-activated receptor-2) is a member of the novel family of proteolytically activated GPCRs (G-protein-coupled receptors) termed PARs (proteinase-activated receptors). Previous pharmacological studies have found that activation o... Read More about Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis.

N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin (2011)
Journal Article
Xiao, Y. P., Morice, A. H., Compton, S. J., & Sadofsky, L. (2011). N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin. Journal of Biological Chemistry, 286(26), 22991-23002. https://doi.org/10.1074/jbc.M110.204271

Proteinase-activated receptor 1 (PAR1) induces activation of platelet and vascular cells after proteolytic cleavage of its extracellular N terminus by thrombin. In pathological situations, other proteinases may be generated in the circulation and mig... Read More about N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin.

TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids (2010)
Journal Article
Sadofsky, L. R., Boa, A. N., Maher, S. A., Birrell, M. A., Belvisi, M. G., & Morice, A. H. (2011). TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids. Pharmacological research : the official journal of the Italian Pharmacological Society, 63(1), 30-36. https://doi.org/10.1016/j.phrs.2010.11.004

The nociceptor TRPA1 is thought to be activated through covalent modification of specific cysteine residues on the N terminal of the channel. The precise mechanism of covalent modification with unsaturated carbonyl-containing compounds is unclear, th... Read More about TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids.

Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents (2010)
Journal Article
Nassini, R., Materazzi, S., Andrè, E., Sartiani, L., Aldini, G., Trevisani, M., …Geppetti, P. (2010). Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents. FASEB Journal, 24(12), 4904-4916. https://doi.org/10.1096/fj.10-162438

Acetaminophen [N-acetyl-p-aminophenol (APAP)] is the most common antipyretic/analgesic medicine worldwide. If APAP is overdosed, its metabolite, N-acetyl-p-benzo-quinoneimine (NAPQI), causes liver damage. However, epidemiological evidence has associa... Read More about Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents.

TRPA1 agonists evoke coughing in guinea pig and human volunteers (2009)
Journal Article
Birrell, M. A., Belvisi, M. G., Grace, M., Sadofsky, L., Faruqi, S., Hele, D. J., …Morice, A. H. (2009). TRPA1 agonists evoke coughing in guinea pig and human volunteers. American Journal of Respiratory and Critical Care Medicine, 180(11), 1042-1047. https://doi.org/10.1164/rccm.200905-0665OC

Rationale: Cough is the most frequent reason for consultation with a family doctor, or with a general or respiratory physician. Treatment options are limited and one meta-analysis concluded that over-the-counter remedies are ineffective. There is als... Read More about TRPA1 agonists evoke coughing in guinea pig and human volunteers.

Transient receptor potential vanilloid-1-mediated calcium responses are inhibited by the alkylamine antihistamines dexbrompheniramine and chlorpheniramine (2008)
Journal Article
Sadofsky, L. R., Campi, B., Trevisani, M., Compton, S. J., & Morice, A. H. (2008). Transient receptor potential vanilloid-1-mediated calcium responses are inhibited by the alkylamine antihistamines dexbrompheniramine and chlorpheniramine. Experimental Lung Research, 34(10), 681-693. https://doi.org/10.1080/01902140802339623

American guidelines, unlike European guidelines, support the use of antihistamines as a first line of treatment for some causes of chronic cough. Transient receptor potential vanilloid-1 (TRPV1) is an ion channel activated by the tussive agents capsa... Read More about Transient receptor potential vanilloid-1-mediated calcium responses are inhibited by the alkylamine antihistamines dexbrompheniramine and chlorpheniramine.

Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4 (2007)
Journal Article
Ramachandran, R., Sadofsky, L., Xiao, Y., Botham, A., Cowen, M., Morice, A., & Compton, S. J. (2007). Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4. American journal of physiology. Lung cellular and molecular physiology, 292(3), L788-L798. https://doi.org/10.1152/ajplung.00226.2006

Human lung fibroblasts express proteinase-activated receptor-1 (PAR 1 ), PAR 2 and PAR 3 , but not PAR 4 . Because PAR 2 has inflammatory effects on human primary bronchial fibroblasts (HPBF), we asked 1) whether the inflammatory mediators TNF-α and... Read More about Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4.