Related Experiment Video

Updated: Jul 4, 2025

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

8.6K

IFNγ: Priming for death

James E Vince1,2

  • 1The Walter and Eliza Hall Institute of Medical Research , Parkville, Australia.

The Journal of Cell Biology
|February 8, 2024
PubMed

Insights

Tumor necrosis factor (TNF) signaling induces cell death when combined with interferon gamma (IFNγ). This study reveals how IFNγ and TNF signaling synergize to activate caspase-8, promoting cell death.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Tumor necrosis factor (TNF) is a key cytokine involved in inflammation and immunity.
  • TNF signaling typically requires overcoming inhibitory signals to induce cell death.
  • Interferon gamma (IFNγ) is known to modulate immune responses and cellular processes.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which IFNγ signaling enhances TNF-induced cell death.
  • To investigate the role of caspase-8 in the synergistic cell death pathway mediated by TNF and IFNγ.
  • To understand how combined cytokine signaling impacts cellular fate decisions.

Main Methods:

  • Cell-based assays to measure cell viability and apoptosis.
  • Western blotting to analyze protein activation, including caspase-8.
  • Stimulation of cells with TNF and/or IFNγ to observe signaling pathway activation.

Main Results:

  • Simultaneous signaling through IFNγ overcomes inhibitory signals in TNF pathways.
  • IFNγ and TNF signaling synergistically activate caspase-8.
  • This synergistic activation leads to efficient execution of apoptosis.

Conclusions:

  • IFNγ plays a critical role in sensitizing cells to TNF-induced apoptosis.
  • The combined action of TNF and IFNγ on caspase-8 is a crucial mechanism for triggering cell death.
  • Understanding this interplay is important for therapeutic strategies targeting cell death pathways.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.2K
Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay05:52

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay

Published on: May 12, 2023

1.3K

Related Concept Videos

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...
6.4K
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
1.6K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
910
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
3.8K
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...
7.4K