Regulation and biosynthesis of Interleukin 10 in macrophage and monocytes involved in inflammation

Abstract

Interleukin 10 has proven itself to be an important regulator of inflammation with a wide range of biological effects. These range from a down regulation of cytokine, chemokine and superoxide production within the macrophage, to an up regulation of immunoglobin secretion in B-cells. However, despite Interleukin 10 being an important anti-inflammatory cytokine, very little is understood about how this cytokine is regulated within the cell. During this study we investigated how Interleukin 10 is regulated in the monocyte and macrophage involved in inflammation. In the first part of the study a sandwich ELIS A was used with FACS analysis, to characterise the profile of Interleukin 10 to purified bacterial lipopolysaccaride and map their secretion to the individual cells involved in inflammation. Using pharmacological specific inhibitors the second messenger pathways were mapped. We have looked at how Interleukin 10 is regulated by the MAP kinase pathways. Using potent and selective MAP kinase inhibitors we have demonstrated in various cell types how inhibition of the p38 and JNK MAP kinase pathways led to a down regulation in Interleukin 10 production. Once the cellular pathways that regulate Interleukin 10 production were worked out, we were able to continue to work further down the regulatory pathways to reach the DNA and begin to investigate which transcription factors are important in Interleukin 10 transcription and translation. Understanding how this important cytokine is regulated can lead to the development of a novel treatment for patients who suffer fi-om tissue destructive and painful inflammation diseases.

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