Related Experiment Video

Updated: Dec 25, 2025

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
07:13

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control

Published on: May 24, 2024

850

Polarization of protease-activated receptor 2 (PAR-2) signaling is altered during airway epithelial remodeling and

Ryan M Carey1, Jenna R Freund1, Benjamin M Hariri1

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.

The Journal of Biological Chemistry
|April 4, 2020
PubMed

Insights

Disease-related airway remodeling alters Protease-activated receptor 2 (PAR-2) polarization in nasal epithelial cells. This shift may increase sensitivity to inhaled proteases and contribute to airway inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Respiratory Medicine

Background:

  • Protease-activated receptor 2 (PAR-2) is typically found on the basolateral side of nasal ciliated cells.
  • Airway diseases can cause epithelial changes, including loss of cilia and squamous metaplasia, potentially affecting PAR-2 localization.
  • Fungal pathogens like Aspergillus fumigatus can activate PAR-2.

Purpose of the Study:

  • To investigate how epithelial remodeling in diseases affects PAR-2 polarization.
  • To determine if altered PAR-2 localization impacts airway cell responses to proteases.
  • To model early disease states and their effect on PAR-2 function.

Main Methods:

  • Used a fluorescent arrestin assay to confirm Aspergillus fumigatus activation of PAR-2.
  • Measured intracellular calcium and cytokine secretion (GM-CSF, TNFα, IL-6) following PAR-2 activation in cell lines and primary cultures.
  • Utilized air-liquid interface (ALI) cultures of primary nasal epithelial cells and explants from nasal polyps and turbinates.
  • Exposed cells to disease-related modifiers (IL-13, cigarette smoke condensate, retinoic acid deficiency) to mimic early disease states.

Main Results:

  • Aspergillus fumigatus activated heterologously expressed PAR-2.
  • PAR-2 activation in squamous cells increased calcium and cytokine release.
  • Differentiated primary nasal ALIs initially responded only to basolateral PAR-2 stimulation.
  • Disease-modified primary cultures responded to both apical and basolateral PAR-2 stimulation.
  • Nasal polyps showed apical calcium responses to PAR-2 stimulation, unlike controls.
  • Isolated ciliated cells retained basolateral PAR-2, suggesting non-ciliated cells mediate apical responses in polyps.

Conclusions:

  • Epithelial remodeling in diseases alters PAR-2 polarization, shifting it from basolateral to allow apical responses.
  • This altered polarization may increase airway sensitivity to inhaled proteases.
  • Non-ciliated cells in remodeled airways likely contribute to aberrant apical PAR-2 signaling.
  • Findings suggest a mechanism for enhanced inflammation in diseases like nasal polyps.
Keywords:
AspergillusG-protein–coupled receptor (GPCR)calciumchloride transportciliacytokineinflammationmucociliary clearancemucosal immunologyprotease

More Related Videos

Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling10:03

Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling

Published on: December 12, 2014

8.4K
Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome04:45

Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome

Published on: June 2, 2022

2.7K

Related Concept Videos

Chronic Obstructive Pulmonary Disease-II: Pathophysiology01:20

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
4.1K
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
7.7K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
16.7K
Asthma-II: Pathophysiology and Classification01:26

Asthma-II: Pathophysiology and Classification

Asthma is a prevalent chronic respiratory condition marked by inflammation and hyperresponsiveness of the airways. Its pathophysiology involves complex interactions among inflammatory pathways, immune responses, and neural mechanisms.
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
3.9K
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
3.4K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.3K