Although originally defined

as a product of Th2 cells, th

Although originally defined

as a product of Th2 cells, this cytokine has now been shown to be produced by a wide set of cell types, including both immune and non-immune cells.2 Reports also demonstrated that one mode of IL-10 regulation is through a feedback loop that curtails excessive inflammatory events. For example, PLX-4720 molecular weight when monocytes are activated with lipopolysaccharide (LPS), a dual cytokine response is induced where pro-inflammatory cytokine production is countered by production of IL-10.3 IL-10 began to flood the literature as a prominent cytokine that works in an autocrine and paracrine manner in response to the inflammatory limb of the immune system to sequester over-activation of pro-inflammatory signals. The capacity of IL-10 as a suppressive agent was bolstered by evidence that Epstein Barr Virus (EBV) contained a genomic insert with homology to the human IL-10 gene. It is hypothesized that EBV acquired the hIL-10 gene through evolution as a means to increase anti-viral responses during

host infection.4 Importantly, research also showed IL-10 could act as a growth factor for lymphoid and myeloid cells under certain conditions, indicating that IL-10 was not solely an immunosuppressant.5 X-ray crystallography confirmed that IL-10 is an acid-sensitive homodimeric protein. Genetic data demonstrate that IL-10 is encoded on chromosome 1 of both mouse and humans, and mIL-10 and hIL-10 are fairly conserved in their amino acid sequences sharing ∼73% homology. hIL-10 and mIL-10 see more span 4.7 kb and 5.1 kb chromosome regions, respectively, yet both active forms are encoded by a series of five exons.2 Recent reports

provide evidence for genetically mediated regulation of IL-10 production. Although several polymorphic changes have been identified in the IL-10 gene promoter, three sites at the −1082 (G/A), −819 (C/T), and −592 (C/A) positions have been best characterized for their regulatory influence. Later in this review, we report that multiple cohort studies show single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene may correlate with increased susceptibility to particular adverse conditions of pregnancy.6–10 The IL-10 receptor is composed of two subunits, IL-10R1 and IL-10R2, known members of the interferon receptor 3-mercaptopyruvate sulfurtransferase family (IFNR). Expression of IL-10R is reported on hemopoietic as well as non-hemopoietic cells.11 IL-10R1 is constitutively expressed on placental cytotrophoblasts.12 IL-10R1 is mainly necessary for the binding of the IL-10 protein while IL-10R2 is specific to initiate a signaling cascade. IL-10R2−/− mice behave like IL-10−/− mice, indicating that the second subunit of the receptor is essential for IL-10 signaling. The most well-described signaling pathway specific for IL-10 binding is that of the Jak/STAT pathway. Briefly, Tyk2 and Jak1 are recruited to the IL-10R1/2 complex.

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