Blocking of Caspases Exerts Anti-Inflammatory Effects on Periodontal Cells

Layla Panahipour1, Lara Cristina Cunha Cervantes1,2, Azarakhsh Oladzad Abbasabadi1

  • 1Department of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria.

Insights

Pan-caspase inhibitor Z-VAD-FMK reduces inflammation in periodontal cells. This study shows blocking caspases lowers inflammatory markers like cytokines and chemokines in response to lipopolysaccharides (LPS) and TNFα.

Area of Science:

  • Oral biology
  • Immunology
  • Pharmacology

Background:

  • Periodontitis involves inflammation linked to caspase activity.
  • Caspases are potential molecular targets for modulating inflammatory responses.
  • Harmful factors like lipopolysaccharides (LPS) and TNFα trigger inflammatory cascades.

Purpose of the Study:

  • To investigate the impact of the pan-caspase inhibitor Z-VAD-FMK on inflammatory responses.
  • To examine the modulation of LPS-induced inflammation in murine cells.
  • To assess TNFα-induced inflammatory responses in human and murine cells.

Main Methods:

  • Utilized the pan-caspase inhibitor Z-VAD-FMK (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoro-methyl ketone).
  • Examined LPS-induced inflammatory response in murine RAW 264.7 cells and primary macrophages.
  • Studied TNFα-induced inflammatory responses in human gingival fibroblasts, HSC2 cells, and murine ST2 cells.

Main Results:

  • Z-VAD-FMK significantly reduced IL1 and IL6 expression in RAW 264.7 cells and macrophages.
  • TNFα-induced CCL2 and CCL5 expression was significantly reduced in murine ST2 cells.
  • Z-VAD-FMK considerably reduced CXCL8 and CXCL10 expression in human gingival fibroblasts and HSC2 cells.

Conclusions:

  • Pharmacological caspase inhibition effectively lowers inflammatory responses in periodontal cells.
  • Blocking caspases reduces the expression of key cytokines and chemokines.
  • Caspase inhibitors represent a potential therapeutic strategy for periodontitis-related inflammation.

Related Concept Videos

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...
12.7K
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...
6.6K
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...
4.0K
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,...
6.0K
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...
6.8K
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...
9.2K