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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., la Marca, G., Andrè, E., Preti, D., Avonto, C., Sadofsky, L., Di Marzo, V., De Petrocellis, L., Dussor, G., Porreca, F., Taglialatela-Scafati, O., Appendino, G., Nilius, B., & 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., Carnini, C., Massi, D., Pedretti, P., Carini, M., Cerbai, E., Preti, D., Villetti, G., Civelli, M., Trevisan, G., Azzari, C., Stokesberry, S., Sadofsky, L., McGarvey, L., Patacchini, R., & 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., Maher, S. A., Freund-Michel, V., & 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.