Interferon beta mediated intracellular signalling traffic in human lymphocytes

A Cataldi1, A Caracino, A Di Baldassarre

  • 1Istituto di Morfologia Umana Normale, Università G. D'Annunzio, Chieti, Italy.

Cellular Signalling
|August 1, 1995
PubMed

Insights

Interferon beta treatment increases diacylglycerol (DG) levels in human lymphocytes by activating phospholipase C and D pathways. This molecular signaling slows down cell growth.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Interferon beta is a crucial cytokine in antiviral and immune responses.
  • Understanding the early molecular events triggered by interferon beta is essential for elucidating its therapeutic effects.
  • Human lymphocytes are key players in the immune system and targets for interferon therapy.

Purpose of the Study:

  • To investigate the early molecular mechanisms activated by human interferon beta in human lymphocytes.
  • To identify key signaling molecules and pathways involved in the cellular response to interferon beta.
  • To correlate early molecular changes with the observed effects on cell growth.

Main Methods:

  • Treatment of human lymphocytes with human interferon beta.
  • Measurement of diacylglycerol (DG) levels.
  • Analysis of phospholipase C and phospholipase D pathway activation.
  • Assessment of phosphatidylinositol-bis-phosphate (PIP2) hydrolysis and phosphatidylcholine (PC) breakdown.

Main Results:

  • A significant early increase in diacylglycerol (DG) levels was observed in interferon beta-treated lymphocytes compared to controls.
  • The DG production was attributed to the sequential activation of phosphoinositide-specific phospholipase C and phospholipase D.
  • Evidence suggests a synergistic role of PIP2 hydrolysis and PC breakdown in the initial response.

Conclusions:

  • The interaction of interferon beta with its cell surface receptors initiates rapid molecular events involving DG production.
  • The activation of phospholipase C and D pathways, alongside PIP2 and PC metabolism, represents an early signaling cascade.
  • These early molecular events contribute to the observed inhibition of human lymphocyte cell growth by interferon beta.

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...
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...
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 are of three kinds RI, RII, and RIII. The RI...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...