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N-cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites (2019)
Journal Article
Chandrabalan, A., McPhillie, M. J., Morice, A. H., Boa, A. N., & Sadofsky, L. R. (2019). N-cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites. European Journal of Medicinal Chemistry, doi:10.1016/j.ejmech.2019.02.074

The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel, which detects noxious stimuli leading to pain, itch and cough. However, the mechanism(s) of channel modulation by many of the known, non-reactive modulators... Read More

Effect of high glucose on human alveolar macrophage phenotype and phagocytosis of mycobacteria (2018)
Journal Article
Vance, J., Santos, A., Sadofsky, L., Morice, A., & Cervantes, J. (2019). Effect of high glucose on human alveolar macrophage phenotype and phagocytosis of mycobacteria. Lung, 197(1), 89–94. doi:10.1007/s00408-018-0181-z

Purpose Diabetes mellitus (DBM) reduces immunological activity and increases susceptibility to various infections, including tuberculosis (TB). Human alveolar macrophage (hAM) functions are altered in DBM. Methods To mimic hyperglycemic conditions i... Read More

Lipid laden macrophages in respiratory disease (2017)
Journal Article
Hart, S. P., Morice, A. H., Sadofsky, L. R., & Hayman, Y. A. (2017). Lipid laden macrophages in respiratory disease. Journal of Neurogastroenterology and Motility, 23(3), 477-478. doi:10.5056/jnm17036

Letter to the editor

Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF) (2017)
Journal Article
Vancauwenberghe, E., Noyer, L., Derouiche, S., Lemonnier, L., Gosset, P., Sadofsky, L. R., …Roudbaraki, M. (2017). Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF). Molecular Carcinogenesis, 56(8), 1851-1867. doi:10.1002/mc.22642

Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, en... Read More

The effects of exogenous lipid on THP-1 cells : an in vitro model of airway aspiration? (2017)
Journal Article
Sadofsky, L. R., Hayman, Y. A., Williamson, J. D., Hart, S. P., & Morice, A. H. (2017). The effects of exogenous lipid on THP-1 cells : an in vitro model of airway aspiration?. Ers Monograph, 3(1), 00026-2016. doi:10.1183/23120541.00026-2016

Chronic inflammatory diseases of the airways are associated with gastro-oesophageal reflux (GOR) and aspiration events. The observation of lipid laden macrophages (LLM) within the airway may indicate aspiration secondary to GOR. The proposed mechanis... Read More

TRPV1 polymorphisms influence capsaicin cough sensitivity in men (2017)
Journal Article
Sadofsky, L. R., Cantero-Recasens, G., Wright, C., Valverde, M. A., & Morice, A. H. (2017). TRPV1 polymorphisms influence capsaicin cough sensitivity in men. Journal of thoracic disease, 9(3), 839-840. doi:10.21037/jtd.2017.03.50

Capsaicin, the hot component of chilli peppers, is a well-known tussive agent, which is regularly used as a tool to study cough and antitussives (1). Capsaicin is known to activate the transient receptor potential vanilloid 1 (TRPV1) cation channel w... Read More

Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis (2016)
Journal Article
Fraser, S. D., Sadofsky, L. R., Kaye, P. M., & Hart, S. P. (2016). Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis. Scientific reports, 6(1), doi:10.1038/srep38689. ISSN 2045-2322

In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes... Read More

Bleomycin increases neutrophil adhesion to human vascular endothelial cells independently of upregulation of ICAM-1 and E-selectin (2016)
Journal Article
Crooks, M. G., Greenman, J., Hart, S. P., Sadofsky, L. R., & Williamson, J. D. (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. doi: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

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). doi:10.1158/0008-5472.CAN-16-1492. ISSN 0008-5472

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

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., Morice, A. H., Compton, S. J., …Morice, A. (2012). Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts. Experimental Lung Research, 38(2), (75-81). doi:10.3109/01902148.2011.644027. ISSN 0190-2148

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

The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system (2011)
Journal Article
Prenen, J., Benemei, S., Nassini, R., Materazzi, S., Vriens, J., Preti, D., …Sadofsky, L. (2012). The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system. Brain, 135(2), (376-390). doi:10.1093/brain/awr272. ISSN 1460-2156

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 pr... Read More

Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis (2011)
Journal Article
Morice, A., Xiao, Y., Compton, S., Sadofsky, L., Morice, A. H., Sadofsky, L. R., …Xiao, Y. P. (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). doi:10.1042/BJ20101958. ISSN 1470-8728

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

N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin (2011)
Journal Article
Morice, A. H., Compton, S. J., Morice, A., Sadofsky, L., Compton, S., & Xiao, Y. P. (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). doi:10.1074/jbc.M110.204271. ISSN 0021-9258

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

TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids (2010)
Journal Article
Morice, A. H., Belvisi, M. G., Birrell, M. A., Maher, S. A., Boa, A. N., Sadofsky, L. R., …Boa, A. (2010). 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. doi: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

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. doi: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

TRPA1 agonists evoke coughing in guinea pig and human volunteers (2009)
Journal Article
Maher, S. A., Freund-Michel, V., Morice, A. H., Sadofsky, L., Belvisi, M. G., Birrell, M. A., …Hele, D. J. (2009). TRPA1 agonists evoke coughing in guinea pig and human volunteers. American Journal of Respiratory and Critical Care Medicine, 180(11), (1042-1047). doi:10.1164/rccm.200905-0665OC. ISSN 1073-449X

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

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. doi: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

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. doi: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