Type 1 interferons

Induction of eIF-2a protein kinase is dependent upon both interferon type and cell type. 

IFN-co represents an additional member of the interferon (type I) family. This 170 amino acid glycoprotein exhibits 50-60 per cent amino acid homology to IFN-as, and appears even more closely related to IFN-x. 

Interferons There are two types of interferons Type I, which includes IFN-a and IFN-jS, and Type II consisting of IFN-y. IFN-a and IFN- 8 have about 30% homology in amino acid sequence. There are two more recently discovered Type I interferons they are called IFN-o and IFN-t. IFN-a and IFN- 8 each have 166 amino acids, and IFN-yhas 143. Both IFN-a and IFN-jS are of single chain structure and bind to the same type of cell surface receptors, whereas IFN-y is a dimer of two identical chains and interacts with another type of receptor. All our cells can produce Type I interferons when infected by viruses, bacteria, and fungi. However, only T cells and natural killer cells can produce... 

Type II interferon. Type I interferon binds to receptor, which in turn activates tyrosine kinase phosphorylation and the subsequent transcription pathway that induces viral resistance. Similarly, Type II interferon binds to another receptor and activates the immune response. 

Interferons are natural proteins produced by the cells of the immune system in response to challenges by foreign agents such as viruses, parasites and tumor cells. Interferons assist the immune response by inhibiting viral replication within host cells. There are three major classes of interferons, interferon type I, interferon type II and interferon type III. They bind to a differen cell surface receptor complexes. The type I interferons in humans are IFN-o , IFN-jS and IFN- >. IFN-y is human interferon type II. All classes of interferon are important in fighting RNA virus infections and endogenous interferons are secreted when abnormally large amounts of dsRNA are found in a cell. 

Interferon Type Commercial Name FDA Approved Indications... 

Among the most highly selective cytokine biopharmaceuticals are the interferons. Interferons are members of a large family of related proteins that may be divided into two categories type I and type II interferons. Type I interferons (i.e., a- and P-interferon) possess antiviral and anti-proliferative properties, whereas type II interferons (i.e., y-interferon) have immunostimulatory activity. Several animal species were examined for their responsiveness to interferons, and with the exception of nonhuman primates, all tested animal species were found to be unresponsive [15]. 

Khine AA, Lingwood CA. Functional significance of globotriao-sylceramide in 2 interferon/ type I interferon receptor mediated... 

Interferons (IFN) were discovered in England by A. Isaacs et al. in 1957. (39) They are low molecular weight glycoproteins acting as cytokines (so-called intercellular mediators) with clear species-specific effects. Interferon type I includes the subtypes IFN-a and IFN-p. They are formed by nearly all cells, whereby IFN-a is mainly produced by monocytes and B-lymphocytes, and IFN-fi mainly by fibroblasts. Both subtypes bind to the same receptor at the target cells and are taken up in the hepa-... 

Interferon type II includes IFN-y, which is probably only produced by T lymphocytes and natural killer cells. IFN-y is of no importance for the therapy of viral hepatitis. (36) (s. p. 702 ) Recently, IFN-o) was isolated, but its biological role is not yet understood. 

Toccaceli F, Rosati S, Scuderi M, lacomi F, Picconi R, Laghi V. Leukocyte and platelet lowering by some interferon types during viral hepatitis treatment. Hepatogastroenterology 1998 45(23) 1748-52. 

Sarkar F H (1982). Pharmacokinetic comparison of leukocyte and Escherrichia coli-derived human interferon type alpha. Antiviral Res. 2 103-106. 

Initially classified according to their cellular origin, the interferons are now typed according to their sequences and their activities. Interferon type I regroups IFN-a (leukocyte IFN) and IFN-P (fibroblast IFN) IFN type II IFN-y (immune IFN). 

MiRNAs are extensively studied in SLE because they seem to play a role in the disease pathogenesis and in the regulation of inflammatory process mediated by cytokines like interferon type I (IFN-I). Because the expression of miRNAs changes in the different phases of SLE disease activity, many groups aim at identifying miRNA(s) that could be used as biomarkers. For example this is the case of miR-146a that has been extensively studied in SLE patients thanks to its correlation with IFN-I production, disease susceptibility and activity. ... 

Hovanessian, A. G., Meurs, E., Aujean, O., Vaquero, C., Stefanos, S. and Falcoff, E., 1980, Antiviral response and induction of specific proteins in cells treated with immune (Type II) interferon analogous to that from viral interferon (Type I)-treated cells. Virology 104 195. 

Interferons [alFN, piFN and ylFN]. Interferons are a family of glycosylated proteins and are cytokines which are produced a few hours after cells have been infected with a virus. Interferons protect cells from viral infections and have antiviral activities at very low concentrations ( 3 x 10 M, less than 50 molecules are apparently sufficient to protect a single cell). Double stranded RNA are very efficient inducers of IFNs. There are three main types of IFNs. The aIFNs are synthesised in lymphocytes and the piFNs are formed in infected fibroblasts. The a and P families are fairly similar consisting of ca 166 to 169 amino acids. Although ylFNs are also small glycosylated proteins (ca 146 amino acids), they are different because they are not synthesised after viral infections but are produced by lymphocytes when stimulated by mitogens (agents that induced cell division). 

Honda K, Takaoka A, Taniguchi T (2006) Type I interferon gene induction by Hie interferon regulatory factor family of transcription factors. Immunity 25 349-360... 

TRIF can also activate IRF-3 leading to the production of type I interferons (EFNs). 

The key end result of TLR signalling is the induction of cytokines. Cytokines are proteins produced during an immune response that allow the maturation, activation and differentiation of effector cells in the immune system. The activation of NFkB and AP-1 by the MyD88 and the TREF dependent pathways leads to the production of proinflammatory cytokines such as IL-6, TNF-a and various chemokines. This pathway can also activate IRF-7 via TLR-7and TLR-9 allowing Type-I interferons to be produced. 

Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5 375— 386... 

Chang, C.C., Konno, S., Wu, J.M. (1991). Enhanced expression of heat shock protein and mRNA synthesis by type I interferon in human HL-60 leukemic cells. Biochem Inti. 24, 369-377. 

Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR (2006) Lambda interferon (IFN-lambda), a type III lEN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 80 4501 509... 

Chang CC, Chen TT, Cox BW, Dawes GN, Stemmer WP, Punnonen J, Patten PA (1999) Evolution of a cytokine using DNA family shuffling. Nat Biotechnol 17 793-797 Chen J, Baig E, Eish EN (2004) Diversity and relatedness among the type I interferons. J Interferon Cytokine Res 24 687-698... 

Dumoutier L, Tounsi A, Michiels T, Sommereyns C, Kotenko SV, Renauld JC (2004) Role of the interleukin (lL)-28 receptor tyrosine residues for antiviral and antiproliferative activity of lL-29/interferon-lambda 1 similarities with type I interferon signaling. J Biol Chem 279 ... 

Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T (2005) IRF-7 is the master reguiator of type-I interferon-dependent immune responses. Nature 434 772-777... 

---