Interferon regulation

Fig. 11.8. Scheme of signal transduction via interferon a. The receptor for interferon a (IFNa) binds and activates the Jak kinases Jakl and Tykl. These phosphorylate the Stat factors Statl and Stat2, leading to formation of Statl-Stat2 heterodimers. The heterodimers are transported into the nucleus and bind to a corresponding DNA element known as ISRE (interferon stimulated response element). Another protein, p48, is also involved in transcription activation of the interferon regulated gene. 

Cohn L, Homer RJ, Niu N, Bottomly K. 1999. T helper 1 cells and interferon regulate allergic airway inflammation and mucus production. J Exp Med. 190 1309-1317. 

Leib DA, Harrison TE, Laslo KM, Machalek MA, Moorman NJ, Virgin HW (1999) Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. J Exp Med 189 663-672 Leib DA, Machalek MA, Williams BR, Silverman RH, Virgin HW (2000) Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene [see comments]. Proc Natl Acad Sci USA 97 6097-6101... 

Cytokines and Immunophilins. A large number of inflammatory mediators and related proteins including the cytokines, colony stimulating factors (CSFs), interferons (IFNs), tumor necrosis factors (TNFs), growth factors (see Growth regulators), neurotrophic factors, and immunophilins are found in the mammalian CNS and appear to play a significant role in CNS function both in development and in aspects of brain homeostasis (40—43). 

Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of ah biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic semm, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. 

The regulation of NHE2 is multifactorial. Chronic exposure to nitric oxide and gamma-interferon decrease NHE2 activity, whereas metabolic acidosis and chronic stimulation with epidermal growth factor (EGF) increase activity. 

Dubois, M.F., Mezger, V., Morange, M., Ferrieux, C., Lebon, P., Bensaude, O. (1988). Regulation of the heat-shock response by interferon in mouse L cells. J. Cell Physiol. 137, 102—109. 

Gendelman HE, Baca LM, Turpin J, Kalter DC, Hansen B, Orenstein JM, Dieffenbach CW, Friedman RM, Meltzer MS (1990) Regulation of HIV rephcation in infected monocytes by IFN-alpha. Mechanisms for viral restriction. J Immunol 145 2669-26676 Giovannini M, Zuccotti GV, Biasucci G, Locatelh V, Riva E (1992) Combined zidovudine and interferon-alpha 2a therapy in children with acquired immune deficiency syndrome. J Int Med Res 20 295-301... 

Kim MO, Suh HS, Brosnan CF, Lee SC (2004) Regulation of RANTES/CCL5 expression in human astrocytes by interleukin-1 and interferon-beta. J Neurochem 90 297-308... 

Dalod M, Hamilton T, Salomon R, et al. Dendritic cell responses to early murine cytomegalovirus infection subset functional specialization and differential regulation by interferon alpha/beta. J Exp Med 2003 197(7) 885-898. 

Wuttge DM, Zhou X, Sheikine Y, et al. CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor expressed in atherosclerotic lesions. Arterioscler Thromb Vase Biol 2004 24(4) 750-755. 

Artis, D., Potten, C.S., Else, K.J., Finkelman, F.D. and Grencis, R.K. (1999b) Trichuris muris. host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-y. Experimental Parasitology 92, 144-153. 

Snapper, C.M. and Paul, W.E. (1987) Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 236, 944-947. 

Aboagye-Mathiesen G et al. Interferon gamma regulates a unique set of proteins in fresh human bladder transitional cell carcinomas. Electrophoresis 1999 20 344-348. 

Biomedical research continues to broaden our understanding of the molecular mechanisms underlining both health and disease. Research undertaken since the 1950s has pinpointed a host of proteins produced naturally in the body that have obvious therapeutic applications. Examples include the interferons and interleukins (which regulate the immune response), growth factors, such as erythropoietin (EPO which stimulates red blood cell production), and neurotrophic factors (which regulate the development and maintenance of neural tissue). 

The term cytokine was first introduced in the mid 1970s. It was applied to polypeptide growth factors controlling the differentiation and regulation of cells of the immune system. The interferons and interleukins represented the major polypeptide families classified as cytokines at that time. Additional classification terms were also introduced, including lymphokines (cytokines such as IL-2 and IFN-y, produced by lymphocytes) and monokines (cytokines such as TNF-a, produced by monocytes). However, classification on the basis of producing cell types also proved inappropriate, as most cytokines are produced by a range of cell types (e.g. both lymphocytes and monocytes produce IFN-a). 

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