Cell death-associated molecular pattern molecules: inflammatory signaling and control

• Grant number: 14/50681-7
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: October 01, 2014
• End date: March 31, 2015
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: José Ernesto Belizario
• Grantee: José Ernesto Belizario
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Apoptosis, necroptosis and pyroptosis are different cellular death programs characterized in organs and tissues as consequence of microbes infection, cell stress, injury and chemotherapeutics exposure. Dying and death cells release a variety of self-proteins and bioactive chemicals originated from cytosol, nucleus, endoplasmic reticulum, and mitochondria. These endogenous factors are named as cell death-associated molecular-pattern (CDAMP), damage-associated molecular-pattern (DAMP) molecules and alarmins. Some of them cooperate or act as important initial or delayed inflammatory mediators upon binding to diverse membrane and cytosolic receptors coupled to signaling pathways for the activation of the inflammasome platforms and NF-kB multi-protein complexes. Current studies show that the non-protein thiols and thiol-regulating enzymes as well as highly diffusible pro-oxidant reactive oxygen and nitrogen species released together in extracellular inflammatory milieu play essential role in controlling pro-and anti-inflammatory activities of CDAMP/DAMP and alarmins. Here we provide an overview of these emerging concepts and mechanisms of triggering and maintenance of tissue inflammation under massive death of cells. (AU)