Related Experiment Video

Updated: Sep 26, 2026

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

Proinflammatory cytokines induce NF-kappaB-dependent/NO-independent chemokine gene expression in MIN6 beta cells

Marshall S Baker1, Xiaojuan Chen, Alizah Rotramel

  • 1Department of Surgery, Division of Transplantation, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

The Journal of Surgical Research
|April 17, 2003
PubMed
Abstract

Insights

Pancreatic beta cells release chemokines like IP-10 and MCP-1 upon inflammatory stimulation. This chemokine gene expression is regulated by NF-kappaB but not by nitric oxide.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Chemokine interactions (IP-10, MCP-1, RANTES) may drive islet transplant rejection.
  • Mechanisms of chemokine gene expression in pancreatic islet cells are not well understood.

Purpose of the Study:

  • To investigate cytokine-induced chemokine gene expression in pancreatic beta cells.
  • To determine the roles of NF-kappaB and nitric oxide (NO) in this process.

Main Methods:

  • Used MIN6 beta-cell line and a clone overexpressing dominant-negative NF-kappaB inhibitor (IkappaBalphaM).
  • Treated cells with cytokines (IL-1beta, TNF-alpha, IFN-gamma) +/- iNOS inhibitor (L-NMMA).
  • Measured chemokine mRNA (IP-10, MCP-1, MIP-1alpha, MIP-1beta, RANTES) and protein levels.

Main Results:

  • Cytokines increased IP-10 and MCP-1 gene expression and protein release in MIN6 cells.
  • NF-kappaB inhibition reduced chemokine expression compared to control MIN6 cells.
  • Nitric oxide synthase inhibition did not affect chemokine gene expression.

Conclusions:

  • Beta cells produce key chemokines (IP-10, MCP-1) in response to inflammation.
  • Cytokine-induced chemokine gene expression is dependent on NF-kappaB signaling.
  • Nitric oxide is not involved in regulating this chemokine gene expression in beta cells.

More Related Videos

Isolated Pancreatic Islet Treatment and Apoptosis Measurement09:36

Isolated Pancreatic Islet Treatment and Apoptosis Measurement

Published on: May 2, 2025

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...
Type I Diabetes II: Pathophysiology01:26

Type I Diabetes II: Pathophysiology

Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular uptake of...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...