The crystal structure of zebrafish IL-22 reveals an evolutionary, conserved structure highly similar to that of human IL-22.

The class II cytokine family consists of small α-helical signaling proteins including the interleukin-10 (IL-10)/IL-22 family, as well as interferons (IFNs). They regulate the innate immune response and in addition have an important role in protecting epithelial tissues. Teleost fish possess a class II cytokine system surprisingly similar to that of humans, and thus zebrafish offers an attractive model organism for investigating the role of class II cytokines in inflammation. However, the evolution of class II cytokines is critical to understand if we are to take full advantage of zebrafish as a model system. The small size and fast evolution of these cytokines obscure phylogenetic analyses based purely on sequences, but one can overcome this obstacle by using information contained within the structure of those molecules. Here we present the crystal structure of IL-22 from zebrafish (zIL-22) solved at 2.1 Å, which displays a typical class II cytokine architecture. We generated a structure-guided alignment of vertebrate class II cytokines and used it for phylogenetic analysis. Our analysis suggests that IL-22 and IL-26 arose early during the evolution of the IL-10-like cytokines. Thus, we propose an evolutionary scenario of class II cytokines in vertebrates, based on genomic and structural data.

Insulin regulation of proliferation involves activation of AKT and ERK 1/2 signaling pathways in vascular smooth muscle cells.

This investigation used primary cultured rat vascular smooth muscle cells (VSMCs) to examine the effect of insulin (INS) on proliferation of VSMCs. In this study, we investigated the role of protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic action of INS in VSMCs. Incubation of rat VSMCs with INS (100 nM) for 10 min resulted in an increase of Akt phosphorylation by 6-fold (p<0.001) and ERK 1/2 phosphorylation by 3-fold (p<0.001). Pretreatment for 15 min with 10 muM of PI3K/Akt inhibitor LY294002 or with 20 muM PD98059, inhibitor of ERK 1/2, significantly reduced INS-stimulated Akt and ERK 1/2 phosphorylation by 76 and 75%, respectively. Prolonged treatment of VSMCs with INS for 24 h did not have an effect on either Akt or ERK1/2 phosphorylation. Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 87% (p<0.001.) The effect of INS on VSMCs proliferation was significantly reduced by 68% by pretreatment with LY294002 (p>0.01) and by 71% (p>0.01) by pretreatment with PD98059. These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to up-regulate proliferation of VSMC's.