Inflammation

Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands. This regulated process then transmits downstream signals through adaptor molecules ending with the caspase cysteine proteases. Caspase 11 has a heterotetrameric structure consisting of two anti-parallel heterodimers. Upon activation, it is cleaved by an autocatalytic mechanism to give rise to individual subunits. This post-translational regulation enables rapid activation. Expression levels of caspase 11 are highest in lung and spleen.

IL-33 is a member of the interleukin family of cytokines that regulates a wide variety of cellular functions. Its receptor is ST2, an IL-1 receptor family member that also acts as a negative regulator of TLR-IL-1R signaling and the IL-1R accessory protein (IL-1RAcP). Receptor binding of IL-33 activates NF-kB and MAP kinases, stimulating downstream expression of TH2-associated cytokines such as IL-4, IL-5 and IL-6.

TNF alpha is a multifunctional proinflammatory cytokine that is part of the tumor necrosis factor (TNF) superfamily. It is mainly secreted by macrophages and causes tumor necrosis when injected into tumor -earing mice. It exists as a multimer of two, three, or five noncovalently linked units. TNF alpha is closely related to the 25kD Tumor Necrosis Factor beta (TNF beta, or lymphotoxin), and both proteins share the same receptors and cellular functions. TNF alpha binds and functions through the TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR receptors.

CCR2 is a receptor for several monocyte chemoattractant proteins (MCP1, MCP3, MCP4) that specifically govern monocyte chemotaxis. CCR2 transduces its downstream signals through increasing intracellular calcium ion levels. For example, MCP1 regulates the monocyte infiltration found in inflammatory diseases such as rheumatoid or the cellular inflammatory response to tumors. CCR2 is also an alternative co-receptor with CD4 for HIV1 infection.

NALP6 belongs to the NLRP family of which function as innate sensors of endogenous and exogenous stress and damage-associated molecular patterns (DAMPs). NLRPs are vital components of the inflammasome which is the cytoplasmic multiprotein complex that coordinates inflammation and cell homeostasis in various type of cells/tissues. NALP6 is one of the newest NLR protein family members and is highly expressed in intestinal epithelium and granulocytes, and to a relatively lower level in T-cells.

Peroxisome proliferators are non-genotoxic carcinogens which are purported to exert their effect on cells by interacting with members of the nuclear hormone receptor superfamily known as peroxisome proliferator activated receptors (PPARs). There are four of these nuclear hormone receptors known to date, and they are ligand-dependent intracellular proteins that stimulate downstream gene transcription of genes such as acyl coenzyme A oxidase and cytochrome P450 (CYP450). Activation occurs through direct binding to specific DNA response elements following activation by an appropriate ligand.

CD73 is a 70kD glycosyl-phosphatidylinositol (GPI)-anchored cell surface molecule that belongs to the 5'-nucleosidase family. It hydrolyzes extracellular nucleotides into membrane permeable nucleosides and is found as both a membrane-bound and soluble molecule. Because it is abundantly expressed on vascular endothelium and some lymphocyte subpopulations, CD73 is a useful lymphocyte differentiation marker. Like many other GPI-anchored molecules, it transmits T-cell activation signals upon ligand engagement.

CD90 is a 25-35kD glycosylphosphatidylinositol (GPI)-linked glycoprotein receptor of the immunoglobulin (Ig) superfamily. It is found on murine T-cells, thymocytes, neuronal cells, granulocytic lineage-derived cells, hematopoietic stem cells, fibroblasts, neurons, and Kupffer's cells. CD90 is often used as a marker for a variety of stem cells and mature neuronal axon processes.  CD90 appears to play a role in cell-cell and cell-matrix interactions and adhesion during synaptogenesis, nerve regeneration, apoptosis and necrosis, inflammation, fibrosis, and metastasis.

CD86 belongs to the immunoglobulin superfamily of proteins that drive innate and adaptive immune responses. It is an 80kD co-stimulatory molecule for the priming and activation of naive and memory T-cells, respectively. CD86 is expressed on activated B- and T- cells, monocytes/macrophages, dendritic cells, and astrocytes.

FLT3 is a Type III tyrosine kinase cell surface receptor found on primitive bone marrow stem cells. The FLT3 ligand is a hematopoietic growth factor that stimulates cells via a set of structurally related tyrosine kinase receptors.  This FLT3 Ligand promotes the differentiation of multiple hematopoietic cell lineages and is expressed as a non-covalently-linked dimer by T-cells, bone marrow, and thymic fibroblasts.