PEPITEM Flashcards
What is PEPITEM?
It is a peptide inhibitor of trans-endothelial migration. It is a multifunctional regulatory peptide. It is a product of 14.3.3 zeta/delta protein, encoded by YWHAZ gene. It plays a role in homeostasis and ensures that the inflammatory response does not run out of control.
What is adiponectin?
Most abundant circulating adipokine. It has metabolic functions like insulin-sensitising. It also has a function in the immune system, it decreases T cell proliferation, decrease APC function and modulate neutrophil function (chemotaxis, apoptosis), it is very good at regulating lymphocyte migration
What is adipokine?
Cytokine produced by adipose tissue (fat cells)
What is the mechanism of action of PEPITEM?
- B cells are recruited on the surface of endothelium but they do not migrate, they activate and bind to the endothelium
- Circulating adiponectin binds to adipoR1/2 on B cells and stimulates them which leads to release of PEPITEM by B cells
- PEPITEM regulates T cell trafficking but it does not directly interact with T cells. It binds to PEPITEM receptor on endothelial cells
- This leads to activation of SPHK1 which generates S1P
- S1P regulates T cells trafficking by switching off beta2 interns not allowing T cells to cross the endothelium
What diseases PEPITEM showed efficacy in treatment?
- Salmonella infection
- Ischemia reperfusion
- Endotoxin induced uveitis
- Sjogren’s disease
- RA
- T1D
What is a significance of PEPITEM and RA and T1D?
AdipoR2 is downregulated in patients with RA and T1D. PEPITEM concentration is also significantly decreased in serum of patients compared to controls. Treatment with synthetic PEPITEM regains the control of T cell trafficking.
What are SVT and QGA?
Independently functional peptides which are just as effective as whole PEPITEM. They regulate leukocyte trafficking in vivo, however, QGA is less successful in regulating eosinophils trafficking and SVT in regulating B cell trafficking
SVT and QGA and neutrophils?
The process by which neutrophil trafficking is regulated by PEPITEM, SVT and QGA is different than for T cells trafficking. You need to treat neutrophils with peptides rather than endothelium and they do not regulate neutrophil migration but they regulate adhesion. They stop adhesion receptors from being unregulated on the surface of neutrophils.
What are peptidomimetics?
Small protein-like chains designated to mimic peptides. They are explored to mimic SVT and QGA for treatment of various diseases and showed efficacy in vitro and in vivo.
What PEPITEM leads to?
It leads to reduced inflammatory cytokines and chemokine release into the inflamed tissue as it reduces IL-6 and TNF-a secretion in macrophages and fibroblasts. It also is acting on bone physiology and pathology and it is a target for bone diseases.
How can be PEPITEM delivered?
It is being explored to deliver PEPITEM via topical treatment in cream and topical treatment on skin gives systemic effects.
