Integrins are transmembrane receptors composed of alpha and beta chains, where beta-integrins are mainly expressed in leukocytes. Leukocytes are white blood cells that act in the immune system to defend our body against foreign pathogens.
NFkB is a transcription factor that plays a role in the expression of genes involved in immune response, inflammation, metastasis, cell survival and more. RelA (p65) is one member of the NFkB mammalian family, alongside other subunits.
Exosomes are spherical to cup-shaped bilayered membrane enclosed nanosize vesicles (30-100 nm) which have the ability to shuttle active cargoes between cells. Johnstone et al. 1987 pioneered in documenting the generation of exosomes in differentiating reticulocytes as a result of the fusion of multi-vesicular endosomes/MVBs with the plasma membrane.
The inflammatory response consists of a complex network of signaling pathways that regulate a diverse set of cytokines, growth factors, adhesion molecules, and transcription factors (1). Of the proinflammatory signaling pathways the NF-kB family is particularly well studied for its role in apoptosis, cancer, and the development and maintenance of the immune system (1). The family consists of the transcription factors p50, p52, RelA (p65), RelB, and c-Rel.
Aside from their important role in apoptosis, caspases also play an important role in inflammatory processes. Humans express four inflammatory caspases: Caspase-1, -4, -5, and -12. Caspase-12 is a 48 kDa protein localized to the ER and involved in the ER stress response. Caspase-12 contains a caspase-associated recruitment domain (CARD) and two catalytic domains, p20 and p10 (1).
Monocyte chemotractant protein-1 (MCP-1), also known as CCL2, is a key chemokine involved in the migration of monocytes and macrophages to sites of active inflammation. It is a member of the C-C/beta family of cytokines, characterized by the Cys-Cys sequence at its N-terminus (1). MCP-1 is tethered to endothelial cells via glycosaminoglycans within the plasma membrane (2). MCP-1 cleavage by MMP-12 is necessary for MCP-1 to interact with its receptor CCR2.
While known for their role in programmed cell death, caspases are also essential for mediating inflammatory responses and innate immunity. Binding of microbial molecules by pattern recognition receptors triggers the formation of the multiprotein inflammasome complex and the activation of caspase-1 (1). Caspase-1 is then able to mediate the activation and secretion of proinflammatory cytokines including interleukin-1. In addition to caspase-1, caspase-11 also plays an important role during the inflammatory response.
Caspases are endoproteases that play important roles in the regulation of cell death and apoptosis. Caspase active sites contain a catalytic cysteine residue essential for the proteolytic cleavage of their substrates at conserved aspartic acid residues (1). Caspases are produced as inactive procaspase monomers in order to regulate their activity. Upon dimerization procaspases are cleaved to produce their active form (1). Caspases are typically grouped by their role in either cell death or inflammation.
Caspase-1 is an enzyme involved in the conversion of interleukin-1 into its active secreted form. Interleukin-1 mediates inflammatory responses during infection and disease. Caspase-1 is recruited to and activated by the inflammasome complex (1). Under normal cellular conditions caspase-1 exists in an inactive pro form. Following stimulation with LPS or various microbial signals procaspase-1 is proteolytically cleaved into 10- and 20-kDa subunits that are enzymatically active (2).
T-cells infiltrating sites of inflammation of the skin typically express the cutaneous lymphocyte-associate antigen (CLA). This antigen is defined by the binding of the monoclonal CLA antibody HECA-452. The CLA antigen is a fucose-containing oligosaccharide and is found on many of the ligands that are recognized by the adhesion proteins P-selectin and E-selectin. CLA is primarily expressed by memory T-cells.