Abstract
Inflammation is a multifaceted defense response of immune system against infection. Chronic inflammation has been implicated as an imminent threat for major human malignancies and is directly linked to various steps involved in tumorigenesis. Inflammatory cytokines, interleukins, interferons, transforming growth factors, chemokines, and adhesion molecules have been associated with chronic inflammation. Numerous cytokines are reported to be aberrantly regulated by different epigenetic mechanisms like DNA methylation and histone modifications in tumor tissues, contributing to pathogenesis of tumor in multiple ways. Some of these cytokines also work as epigenetic regulators of other crucial genes in tumor biology, either directly or indirectly. Such regulations are reported in lung, breast, cervical, gastric, colorectal, pancreatic, prostate, and head and neck cancers. Epigenetics of inflammatory mediators in cancer is currently subject of extensive research. These investigations may help in understanding cancer biology and to develop effective therapeutic strategies. The purpose of this paper is to have a brief view of the aberrant regulation of inflammatory cytokines in human malignancies.
Highlights
Inflammation is a complex defense response of immune system, attempted to neutralize an insult and reestablish normal tissue structure and function [1]
About 25% of all cancers are connected to chronic inflammation, which is linked to various stages of tumorigenesis including cellular transformation, tumor progression, endurance, propagation, invasion, angiogenesis, and metastasis [12,13,14]
Epigenetic regulation is the mechanism by which chromatin undergoes multiple types of alterations including histone modifications and DNA methylation
Summary
Inflammation is a complex defense response of immune system, attempted to neutralize an insult and reestablish normal tissue structure and function [1]. Inflammation is characterized by redness, swelling, and pain and sometimes failure of function It is mainly mediated and regulated by inflammatory cytokines. About 25% of all cancers are connected to chronic inflammation, which is linked to various stages of tumorigenesis including cellular transformation, tumor progression, endurance, propagation, invasion, angiogenesis, and metastasis [12,13,14]. The survival and growth of the initiated cells are prerequisite for tumor development Many inflammatory mediators such as interleukins, eicosanoids, and chemokines are able to motivate the propagation of both normal and cancer cells [18]. The active or silent gene states are controlled by the processes of addition or removal of chemical modifications in the chromatin [28, 29] These modifications include DNA methylation and a variety of posttranslational histone modifications (acetylation, methylation, phosphorylation, etc.). The current review is focused on epigenetic regulation of different inflammatory cytokines involved in various human malignances with emphasis on aberrant methylation
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