Pleiotropy On Chemokines

CYTOKINES

Cytokines are low-molecular weight regulatory proteins or glycoproteins secreted predominantly by leukocytes and various other cells (e.g., endothelial cells, epithelial cells and fibroblasts) in the body. They composed of interleukins (ILs), interferons (IFNs), growth factors, colony stimulating factors (CSFs), the tumor necrosis factor (TNF) family, and chemokines. Cytokines can function in an autocrine, paracrine, or endocrine manner for stimulating or suppressing the activity of target cell populations (Fitzgerald et al., 2001). Their part is natural in immune modulators; many cytokines have been identified as appropriate therapeutic agent for the treatment of a number of infectious, inflammatory, and malignant autoimmune diseases.

Cytokines and their receptors exhibit very high affinity for each other. Cytokines exhibit the attributes of pleiotropy in which one cytokines has the ability to act on many different cell types to mediate diverse and sometimes opposing effects. Another important property of cytokine signaling is its degree of redundancy, in which various cytokines have the similar functional effects. This redundancy may have the therapeutic manipulation of cytokines somewhat challenging since modification of one cytokine can be compensated by

Both involved in inflammatory processes and belong to TNF receptors superfamily. For the initiation of receptor-induced signaling pathways, the receptors require cytoplasmic proteins (RM et al. 2001). The two receptors having molecular masses 55 and 75 kDa, both the receptors exist in soluble form (Wallach et al.). The both soluble receptors present at high concentration in plasma of normal healthy individual and in case of pathological situations, such as inflammatory disorders and renal failure, even higher concentration is observed (Chouaib et al. 1991). The affinity of TNF receptor 2 (TNFR-2) is five folds more than the TNFR-1. TNFR-1 is expressed on all cell types, while the expression of TNFR-2 restricted to immune cells only. The major difference between the two receptors is presence of death domain (DD) on TNFR-1 only. This is the reason that TNFR-1 is an important member of death receptor family which has capability to induce apoptotic cell death; it also has ability to induce cell survival signals (Horssen et al., 2006). In recent year, understanding of these two super families has rapidly advanced with development in protein crystallography and through the study of several diseases directly associated with gene mutations which lead to substitution of amino acids in TNFR1, Fas/FasL, TACI, RANK, DR4/5 etc. proteins. Currently 19 ligands and 30