Recombinant Human IL-28B/IFN-lambda 3

Interleukin-28B (also named interferon-lambda 3, IFN-lambda 3), IL-28A (IFN-lambda 2) and IL-29 (IFN-lambda 1) are type III interferons that are class II cytokine receptor ligands ^[1-4]. They are distantly related to members of the IL-10 family and type I IFN family ^{[1- 4]}. Human IL-28B cDNA encodes a 200 amino acid (aa) protein with a 25 aa signal peptide and a 175 aa mature protein that lacks N-glycosylation sites. Mature human IL-28B shares 64% and 75% aa sequence identity with mouse and canine IL-28B, respectively, and is active across species ^[5]. Human IL-28B shares 94% and 69% aa identity with human IL -28A and IL-29, respectively ^[4]. Type III interferons are widely expressed, but are mainly produced by antigen presenting cells in response to viruses and double -stranded RNA that interact with Toll-like receptors or RIG-1 family helicases ^[2-6]. They signal through a widely expressed receptor that is a heterodimer of the IL-10 receptor beta (IL-10 R beta) and IL-28 receptor alpha (IL-28 R alpha; also called IFN-lambda R1) ^{[2, 3, 7, 9]}. Interaction of either type I or type III IFNs with their receptors activates similar pathways, including JAK tyrosine kinase activation, STAT phosphorylation and formation of the IFN-stimulated regulatory factor 3 (ISGF-3) transcription factor complex ^[1-3]. Both type I and III IFNs induce anti-viral activity and up-regulate MHC class I antigen expression ^[2-6]. Cell lines responsive to type III IFNs are also responsive to type I IFNs, but in general, higher concentrations of type III IFNs are needed for similar in vitro responses ^[8]. In vivo, however, type III IFNs enhance levels of IFN-gamma in serum, suggesting that the robust anti-viral activity of type III IFNs may stem in part from activation of the immune system ^{[5, 7]}. Anti-proliferative and antitumor activity in vivo has also been shown for type III IFNs ^[9-11]. 

Reference

[1]. Chen, Q. et al. (2006) Vitam. Horm. 74:207.

[2]. Sheppard, P. et al. (2003) Nat. Immunol. 4:63.

[3]. Kotenko, S.V. et al. (2003) Nat. Immunol. 4:69.

[4]. Bartlett, N.W. et al. (2005) J. Gen. Virol. 86:1589.

[5]. Ank, N. et al. (2006) J. Virol. 80:4501.

[6]. Onoguchi, K. et al. (2007) J. Biol. Chem. 282:7576.

[7]. Siebler, J. et al. (2007) Gastroenterology 132:358.

[8]. Meager, A. et al. (2005) Cytokine 31:109.

[9]. Lasfar, A. et al. (2006) Cancer Res. 66:4468.

[10]. Sato, A. et al. (2006) J. Immunol. 176:7686.

[11]. Zitzmann, K. et al. (2006) Biochem. Biophys. Res. Commun. 344:1334.