Cytokine immunoglobulin family

One common feature of the cytokine receptor family, including the IL-6 family, is that its members contain immunoglobulin (Ig)-like domains, of which the structures are similar to that of Ig, in the extracellular site of each subunit (Bazan 1991). Near the C-terminal end of the second domain ( C-terminal domain), there is a cytokine receptor family consensus sequence, W(Trp)-S(Ser)-X(a variable residue)-W-S. 

Fig. 3.1 Families of cytokine receptors the cytokine receptors are classified into five major families immunoglobulin superfamily receptors, type I cytokine receptors, type II cytokine receptors, TNF-like receptors and chemokine receptors. The drawings illustrate their general biochemical structure (see Color Insert)...

The IL-1 family is also called the immunoglobulin superfamily. The IL-IR family includes both transmembrane and soluble proteins withan immunoglobuhn-like structure. There are four primary members of the IL-1 family IL-la, IL-1 [3, IL-18, and IL-lRa. IL-1 ligands (IL-la and IL-1[3, collectively referred to as IL-1) are potent pro-inflammatory cytokines that induce genes associated with inflammation and autoimmune disease. IL-lRa, on the other hand, is the specific receptor antagonist for IL-la and IL-1 [3 but not for IL-18. 

The inflammatory process initiated by locally produced proinflammatory cytokines induce or enhance the expression of several adhesion molecules [7,8,39,103]. The adhesion of leukocytes to the endothelial surface and their subsequent migration from the microvessels into the brain parenchyma are mediated by a variety of molecules located on the surface of both leukocytes and endothelial cells [7]. Adhesion molecules are divided into four main families integrins, the immunoglobulin superfamily, cadherins, and selectins [115]. Under normal conditions, there is little or no cell-surface expression of adhesion molecules [116]. Inflammatory processes, such as cerebral ischemia induce their expression with the upregulation mediated by cytokines [7]. They are glycoprotein in nature and are the anchors that mediate the attachment of leukocytes [117]. 

The eukaryotic transcription factor NF-kB was identified as a protein that binds specifically to a decameric DNA sequence (ggg ACT TTC C), within the intronic enhancer of the immunoglobulin kappa light chain in mature B and plasma cells, but not pre-B cells [32, 33]. This transcription factor consists of homo- or heterodimers of different subunits which are members of a family of structurally related proteins (Rel/NF-icB proteins). NF-kB has been detected in most cell types, and specific NF-kB binding sites have been identified in promoters and enhancers of numerous inducible genes. Thus, it has been shown that NF-kB plays a pivotal role in the coordinated transactivation of many genes involved in cytokine-mediated inflammation. 

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