Related Experiment Videos

Regulation of apoptosis of synovial fibroblasts

J D Mountz1, H G Zhang

  • 1Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham Veterans Administration Medical Center, Birmingham, Ala., USA. John.Mountz@ccc.uab.edu

Current Directions in Autoimmunity
|January 17, 2002
PubMed

Insights

Defects in apoptosis, or programmed cell death, are not the cause of human autoimmune diseases. Studies show excessive immune cell death and decreased parenchymal cell death, suggesting new therapeutic targets.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The Fas gene mutation in lpr mice causes autoimmune disease due to defective T and B cell apoptosis.
  • This defect leads to immune cell accumulation and impaired immune response regulation.
  • This suggested a potential role for apoptosis defects in human autoimmune diseases.

Purpose of the Study:

  • To investigate the role of apoptosis defects in human autoimmune diseases.
  • To analyze proapoptotic and antiapoptotic pathways in patients with autoimmune conditions.
  • To determine if immune cell apoptosis defects contribute to autoimmune disease pathogenesis.

Main Methods:

  • Analysis of proapoptotic genes (Fas, Fas ligand, Bcl-X, caspases) and antiapoptotic pathways.
  • Examination of genetic defects at RNA, protein, and functional levels in human autoimmune disease patients.
  • Assessment of peripheral blood mononuclear cells (PBMCs) and synovial cells (RASF) apoptosis.

Main Results:

  • Most studies indicate excessive apoptosis of PBMCs in human autoimmune diseases.
  • This finding suggests that defective immune cell apoptosis is not the primary cause of human autoimmune disease.
  • Some evidence points to decreased apoptosis in parenchymal cells like RASF, which exhibit hyperplasia.

Conclusions:

  • Human autoimmune diseases are not caused by defective apoptosis of immune cells.
  • Therapeutic strategies may need to focus on promoting apoptosis in specific cell types, such as RASF.
  • Modulators of apoptosis, including gene therapy and compounds like wortmannin, show potential for treating conditions involving RASF hyperplasia.

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
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 by phagocytes.
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...