400 Cathepsin S Induces Inflammation and Pain via Biased Agonism of PAR2 and TRPV4

Zhao, Peishen; Barlow, Nicholas; Lieu, TinaMarie; Metcalf, Matthew; Veldhuis, Nicholas A.; Jensen, Dane D.; Kočan, Martina; Sostegni, Silvia; Lindström, Erik; Korbmacher, Christoph; Bunnett, Nigel W.

doi:10.1016/s0016-5085(14)60308-5

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many of the studies we will review below use PAR-AP to study PAR-mediated effects, since unlike natural proteases they do not induce PARindependent effects. Among PARs, PAR 2 has a wide expression pattern (11) and has been linked to inflammation in the skin (12), gastrointestinal tract (13) and lungs (14), as well as in inflammatory pain (15).…”

Section: Introductionmentioning

confidence: 99%

Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity

2022

View full text Add to dashboard Cite

PAR2, a receptor activated by serine proteases, has primarily pro-inflammatory roles in the airways and may play a role in asthma pathogenesis. PAR2 exerts its effects in the lungs through activation of a variety of airway cells, but also activation of circulating immune cells. There is evidence that PAR2 expression increases in asthma and other inflammatory diseases, although the regulation of PAR2 expression is not fully understood. Here we review the available literature on the potential role of PAR2 in asthma pathogenesis and propose a model of PAR2-mediated development of allergic sensitization. We also propose, based on our previous work, that PAR2 expression on peripheral blood monocyte subsets has the potential to serve as a biomarker of asthma severity and/or control.

show abstract

Section: Introductionmentioning

confidence: 99%

Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity

2022

View full text Add to dashboard Cite

show abstract

“…Cloning of the seven-transmembrane G protein-coupled receptor (GPCR) proteaseactivated receptor 2 (PAR2) [1] allowed a detailed investigation of its role in a number of physiological and pathophysiological processes, including acute and chronic inflammation and hypersensitivity induction [2][3][4][5][6][7]. Numerous endogenous proteases target PAR2 to cleave the extracellular amino terminus at canonical cleavage sites (trypsin and mast cell tryptase) [8] to activate canonical pathways of GPCR signaling or at distinct sites (neutrophil elastase or macrophage cathepsin S) to activate the biased mechanisms [7,9,10]. Several synthetic PAR2-activating peptides (PAR2 AP) were developed, and in our experiments, we used SLIGKV-NH2, which corresponds to the tethered ligand domain and mimics the canonical mechanism of activation by the endogenous activators [11,12].…”

Section: Introductionmentioning

confidence: 99%

Spinal PAR2 Activation Contributes to Hypersensitivity Induced by Peripheral Inflammation in Rats

Mrózková

Spicarova

Paleček

2021

IJMS

View full text Add to dashboard Cite

The mechanisms of inflammatory pain need to be identified in order to find new superior treatments. Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) are highly co-expressed in dorsal root ganglion neurons and implicated in pain development. Here, we examined the role of spinal PAR2 in hyperalgesia and the modulation of synaptic transmission in carrageenan-induced peripheral inflammation, using intrathecal (i.t.) treatment in the behavioral experiments and recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs and eEPSCs) in spinal cord slices. Intrathecal PAR2-activating peptide (AP) administration aggravated the carrageenan-induced thermal hyperalgesia, and this was prevented by a TRPV1 antagonist (SB 366791) and staurosporine i.t. pretreatment. Additionally, the frequency of the mEPSC and sEPSC and the amplitude of the eEPSC recorded from the superficial dorsal horn neurons were enhanced after acute PAR2 AP application, while prevented with SB 366791 or staurosporine pretreatment. PAR2 antagonist application reduced the thermal hyperalgesia and decreased the frequency of mEPSC and sEPSC and the amplitude of eEPSC. Our findings highlight the contribution of spinal PAR2 activation to carrageenan-induced hyperalgesia and the importance of dorsal horn PAR2 and TRPV1 receptor interactions in the modulation of nociceptive synaptic transmission.

show abstract

400 Cathepsin S Induces Inflammation and Pain via Biased Agonism of PAR2 and TRPV4

Cited by 2 publications

References 0 publications

Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity

Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity

Spinal PAR2 Activation Contributes to Hypersensitivity Induced by Peripheral Inflammation in Rats

Contact Info

Product

Resources

About