AbuArish_CPPS325_March17_2025_Lecture 5_Upload (1) Flashcards
What is the role of CFTR in cystic fibrosis?
CFTR regulates inflammation and contributes to dysregulation in hyperinflammatory pulmonary diseases
CFTR dysfunction leads to hyperinflammation in cystic fibrosis cases.
What is the inflammation-infection cycle in cystic fibrosis?
A cycle where inflammation leads to infections and vice versa, exacerbating disease symptoms
This cycle is critical to understanding cystic fibrosis pathology.
What is the NLRP3 inflammasome?
A protein complex that plays a crucial role in the inflammatory response, particularly in macrophages
NLRP3 activation leads to the production of pro-inflammatory cytokines.
What triggers the formation of the NLRP3 inflammasome?
Pathogenic stimuli such as Lipopolysaccharide (LPS) and danger signals like ATP
These signals lead to the aggregation of NLRP3 and ASC into a cytoplasmic complex.
How does caspase-1 contribute to inflammation?
Caspase-1 activates pro-inflammatory cytokines IL-1β and IL-18 and cleaves GSDMD for cytokine release
This process is essential for the inflammatory response.
What is the effect of cigarette smoke on NLRP3 inflammasome formation in HAECs?
Cigarette smoke extract leads to the aggregation of ASC and NLRP3 into cytoplasmic clusters in HAECs
These clusters differ from typical NLRP3 inflammasomes seen in macrophages.
What are stress granules (SGs)?
Membraneless cytoplasmic aggregates of proteins and mRNA that form in response to cellular stress
SGs play a role in cytoprotection and the regulation of gene expression.
What is the Integrated Stress Response (ISR) pathway?
A cellular response mechanism to stress that involves upregulation of protective genes
Key components include eIF2α, HRI, PKR, PERK, and GCN2.
What is the relationship between ceramides and CFTR?
Ceramides regulate CFTR stability and distribution, influencing inflammation
In cystic fibrosis, CFTR function loss leads to ceramide generation, affecting inflammation.
Fill in the blank: The activation of the NLRP3 inflammasome leads to the release of _______.
[pro-inflammatory cytokines]
True or False: Inflammasomes in HAECs form in response to LPS and ATP treatment.
False
No inflammasome formation is observed in HAECs under these conditions.
What is the significance of GSDMD in the inflammatory process?
GSDMD forms pores in the membrane for the release of cytokines
This is a crucial step in the inflammatory response.
In cystic fibrosis, what leads to inflammation dysregulation?
Loss of CFTR function induces hyperinflammation
This dysregulation is evident in CF airways.
What does the formation of NLRP3/ASC/Caspase-1 aggregates resemble?
Stress granules
This suggests a potential link between inflammasome activity and stress responses.
What is the role of inflammatory triggers like Thapsigargin in CFTR function?
They modulate membrane CFTR distribution and downregulate its function
This contributes to the inflammatory state in cystic fibrosis.
What happens to inflammasome proteins in HAECs when exposed to cigarette smoke?
They aggregate into irregular shaped cytoplasmic clusters
This is different from the formation in macrophages.
What does PERK stand for?
PKR-like ER kinase
What does GCN2 stand for?
General control non-derepressible 2
What is the Integrated Stress Response (ISR) Pathway?
A cellular response involving Stress Granules (SGs)
What are Stress Granules (SGs)?
Membran-less cytoplasmic protein-mRNA aggregates that assemble in response to cell exposure to stress
What effect does the formation of Stress Granules have on protein synthesis?
It inhibits global protein synthesis
What does the cell focus on during Stress Granule formation?
Upregulating antioxidant protein synthesis
What happens to Stress Granules following stress neutralization?
They undergo disassembly
What influences the assembly/disassembly timelines of Stress Granules?
The type and intensity of the stressor
True or False: Stress Granules are static and do not change in response to stress.
False
Fill in the blank: NLRP3 inflammasome proteins are sequestered inside _______.
SGs
What is one role of SG formation in healthy HAECs?
How do CF HAECs respond to CSE?
