Abstract
One of the human body’s initial responses to stress is the adrenal response, involving the release of mediators that include adrenaline and glucocorticoids (GC). GC are involved in controlling the inflammatory and immune response mechanisms. Of these, the molecular mechanisms that contribute to anti-inflammatory effects warrant more investigation. Previously, we found that GC induced GILZ (glucocorticoid-induced leucine zipper) quickly and widely in thymocytes, T lymphocytes, and other leukocytes. GILZ regulates the activation of cells and is an essential mediator of endogenous GC and the majority of GC anti-inflammatory effects. Further research in this regard could lead to the development of an anti-inflammatory treatment that yields the therapeutic outcomes of GC but without their characteristic adverse effects. Here, we examine the mechanisms of GILZ in the context of GC. Specifically, we review its role in the proliferation and differentiation of cells and in apoptosis. We also examine its involvement in immune cells (macrophages, neutrophils, dendritic cells, T and B lymphocytes), and in non-immune cells, including cancer cells. In conclusion, GILZ is an anti-inflammatory molecule that could mediate the immunomodulatory activities of GC, with less adverse effects, and could be a target molecule for designing new therapies to treat inflammatory diseases.
Highlights
The stress response is an important complex of mechanisms aimed at regulating numerous body functions essential for survival
Other than being an important mediator of endogenous GC, GILZ mediates most of the anti-inflammatory effects of exogenous GC, which could give rise to new anti-inflammatory treatments that mimic the curative effects of GC while not inducing typical GC adverse effects
This effect was supported by the observation that GILZ depletion rendered GILZ-KO neutrophils incapable of upregulating ANXA-1, a pivotal protein for GC to prevent neutrophil migration into inflamed tissues
Summary
The stress response is an important complex of mechanisms aimed at regulating numerous body functions essential for survival. Among the first responses is the adrenal response, involving the production of a series of mediators, including adrenaline and glucocorticoids (GC) released from the adrenal cortex These are important mediators that can affect the many functions of the organism by acting on practically all tissues. GITR is not up-regulated in normal cells in vivo, it is normally expressed in many cells and tissues, including, for example, lymphocytes, keratinocytes and neurons [2,3] and plays a role in infections and the inflammatory/immune processes. Other than being an important mediator of endogenous GC, GILZ mediates most of the anti-inflammatory effects of exogenous GC, which could give rise to new anti-inflammatory treatments that mimic the curative effects of GC while not inducing typical GC adverse effects These detrimental effects limit any chronic GC therapy, as first shown in different inflammatory colitis models [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
