Cytokine Interactions

IDDM is a disease in which /3 cells of islets are selectively destroyed. How does a nonspecific effector molecule (nitric oxide) mediate the selective destruction of the /3 cell We propose that the specificity of cytokine interactions with the /8 cell, and the intrinsic sensitivity of the /3 cell to oxidative damage relative to other endocrine cells may impart this selective destruction. In rats the effects of lL-1 appear to be specific to the /3 cell. lL-1 induces iNOS expression and the overproduction of nitric oxide by /3 cells, but does not induce expression of iNOS or nitric oxide formation in other islet endocrine or nonendocrine cells of the... 

It is important to emphasize that cytokine interactions with target cells often result in the release of a cascade of different endogenous cytokines, which exert their effects sequentially or simultaneously. For example, IFN-7 exposure increases the number of cell surface receptors on target cells for TNF- . Therapy with IL-2 induces the production of TNF- , while therapy with IL-12 induces the production of IFN-7. 

Each interface contains 11 or 12 hydrogen bonds or salt bridge interactions. Although the GH/GHR complex buries more surface area into its interface, it stiU contains only 12 specific interactions. Three of the IFN-7/ IFN-7RI interactions occur between mainchain atoms in the AB loop of IFN-7 and the L2 loop of IFN-7RI. In addition to the 12 receptor-cytokine interactions, seven water molecules bridge the donor and acceptor groups of IFN-7 and IFN-7RI via hydrogen bonds (Randal and Kossiakoff, 2001). Since the B-factors for the water and protein atoms in the complex are essentially the same, the water molecules are considered to be an integral part of the interface. The presence of ordered water molecules in the IFN-7/IFN-7RI interface is not likely unique, since the IL-lO/IL-lORl interface is even more polar. However, the poorer diffraction quality of IL-10 complex crystals ( 2.9A versus 2.0A) obtained at this time prevents a detailed description of the interfacial waters. The water molecules in the... 

Each class of growth factors and cytokines interacts with a special class of receptors and recruits its own set of transducers and transcription factors. Moreover, TGF-P and... 

Pawluczyk IZ, Flarris KP. Cytokine interactions promote synergistic fibronectin accumulation by mesangial cells. Kidney Int 1998 ... 

Wegmann TG, Lin H, Guilbert L, Mosmann TR Bidirectional cytokine interactions in the maternal-fetal relationship Is successful pregnancy a Th2 phenomenon Immunol Today 1993 14 353-356. 

The arachidonic acid present in membrane phospholipids is released from the lipid bilayer as a consequence of the activation of membrane-bound phospholipase A2 or C (see Fig. 33.31 and Fig. 35.2). This activation occurs when a variety of stimuli (agonists), such as histamine and the cytokines, interact with a specific plasma membrane receptor on the target cell surface. Phospholipase A2 is specific for the sn-2 position of phosphoacylglycerols, the site of attachment of arachidonic acid to the glycerol moiety. Phospholipase C hydrolyzes phosphorylated inositol... 

One important effect of cytokines on cells is the induction of the release of other cytokines, thereby inducing a cascade of cytokine interaction. IL-2, for example, induces the release of IFNy by T cells that induces the release of CXCLIO (interferon-inducible protein-10 IP-10) and other mediators. Cytokine effects are not isolated events, but are part of a complex cytokine network. ... 

Davis GS, Pfeiffer LM, Leslie KE, Hemenway DR. Macrophage-lymphocyte cytokine interactions in silicosis. Chest 1996 109 849-850. 

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