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IL-10 is known as an-inflammatory cytokine and produced by various cells including immune cells like T and B cells, and tumor cell lines. Several reports have demonstrated that IL-10 is involved in many important physiological processes like the inhibition of antigen presentation and the release of proinflammatory cytokines, regulation of the proliferation and differentiation of several immune cell types.
It has been shown that IL-10 serve as an anti-inflammatory cytokine via binding with IL-10 receptor, which is expressed on a variety of cells, particularly immune cells. Previous structure studies have shown that IL-10R is composed of 2 α chains and 2 β chains. Those two chains have distinct role that α binds with IL-10, and β works in signal transduction with access to IL-10. Studies have shown that binding of IL-10 to IL-10 receptor results in activation of kinase-1 and tyrosine kinase-2, which leads to phosphorylation of IL-10 receptor in turn. Phosphorylated IL-10R binds with signal transducer and activator of transcription (STAT)-3, resulting in phosphorylation of STAT3 by receptor-associated Janus activated kinases and the activation of downstream target genes such as the expression of suppressor of cytokine signaling (SOCS)-3 gene, which inhibits the production of proinflammatory cytokines and JAK/STAT-dependent signaling, and ultimately the expression of anti-inflammatory effectors. The whole signaling pathway is shown as Figure 1.
Figure 1. Signaling pathway of IL-10. (Kumar S, et al.)
Roles of IL-10 in related diseases
Accumulating evidences have demonstrated that IL-10 is implicated with various diseases including irritable bowel syndrome (IBS), obesity, Alzheimer’s disease (AD), cervical carcinoma and so on. Thus, it might be a potent anti-inflammatory biological therapy target for those diseases.
IL-10 and AD
Recently, some reports have considered that an imbalance between pro-inflammatory and anti-inflammatory cytokines may be an important phenomenon in AD. Thus, IL-10, an anti-inflammatory cytokine, must plays a crucial role in AD. Indeed, studies with transgenic AD mouse models have demonstrated that IL-10 significantly reduced neuroinflammation, enhanced neurogenesis and improved spatial cognitive dysfunction. Those findings indicated that IL-10 may have a positive function in neuroinflammation, cognitive dysfunction and neurodegeneration. Moreover, several studies also focus on the relationship between the functional polymorphisms of the IL-10 gene and AD, and conclude that the IL-10 polymorphisms are an additive and independent risk factor for AD.
IL-10 and cervical carcinoma
Studies have found that IL-10 production can be induced and maintained by various cells such as infected keratinocytes, some subsets of dendritic cells (DC) and tumor cells in the condition of HPV infection. Additionally, a number of data have shown that the HPV E2, E6 and E7 proteins act over IL-10 gene transcription, leading to the increasing of IL-10 levels, while IL-10 stimulates HPV E6 and E7 expression like Figure 2. Therefore, there is a vicious cycle between IL-10 and HPV, which might be contributed to the progression of a simple HPV infection to SIL or cervical cancer.
Figure 2. The interplay between IL-10 and HPV. (Berti F C, et al.)
In addition to the diseases mentioned above, IL-10 also has a complex regulation in others virus infection. A better understanding about IL-10 effects on the different physiological and pathological processes will be contributed to the further studies that IL-10 is function as a therapeutic target.