Related Experiment Video

Updated: Jun 25, 2026

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

CFTR is a negative regulator of NFkappaB mediated innate immune response

Neeraj Vij1, Steven Mazur, Pamela L Zeitlin

  • 1Department of Pediatric Respiratory Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America. nvij1@jhmi.edu

Plos One
|February 28, 2009
PubMed
Abstract

Insights

Cystic fibrosis transmembrane conductance regulator (CFTR) normally suppresses inflammation by down-regulating NFkappaB signaling. CFTR

Area of Science:

  • Cell Biology
  • Immunology
  • Respiratory Medicine

Background:

  • Dysfunctional CFTR in cystic fibrosis airways leads to elevated NFkappaB-mediated IL-8 signaling, promoting inflammation.
  • The precise role of CFTR in regulating inflammatory signaling pathways remains under investigation.

Purpose of the Study:

  • To investigate the hypothesis that wild-type CFTR (wt-CFTR) down-regulates NFkappaB-mediated IL-8 secretion.
  • To determine if CFTR's localization to cell surface lipid rafts is essential for its anti-inflammatory function.

Main Methods:

  • Transient and stable expression of wt-CFTR in HEK293 and CFBE41o- cells to assess IL-8 and NFkappaB promoter activity.
  • Treatment with methyl-beta-cyclodextrin to disrupt lipid rafts and CFTR-172 inhibitor to block CFTR channel function.
  • In vivo studies using CFTR knockout (CFKO) mice compared to wild-type controls, assessing survival, body weight, and inflammatory markers after LPS challenge.

Main Results:

  • Wt-CFTR expression significantly suppressed basal and IL1beta-induced IL-8 and NFkappaB promoter activities in cell lines.
  • Disruption of lipid rafts or inhibition of CFTR channel function increased IL-8 and NFkappaB reporter activities.
  • CFKO mice exhibited decreased survival, reduced body weight, and elevated IL-1beta and phosphorylated IkappaB levels compared to controls.

Conclusions:

  • CFTR acts as a negative regulator of the NFkappaB-mediated innate immune response.
  • CFTR's localization to lipid rafts is crucial for its role in controlling airway inflammation.
  • These findings highlight CFTR's importance in maintaining immune homeostasis in the airways.

More Related Videos

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes10:05

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...