Dynamic regulation of the proinflammatory cytokine, interleukin-1beta: molecular biology for non-molecular biologists

Abstract

Interleukin-1beta (IL-1beta) is a key mediator and modulator of a wide array of physiological responses important for survival. It is created by a variety of cell types, including immune cells, glia, and neurons. It is a very potent biological molecule, acting both at the periphery as well as within the central nervous system. The production and release of IL-1beta is tightly regulated by far more complex processes than previously thought. An appreciation of this complexity is necessary for proper interpretation of apparent contradictions in the literature where different aspects of IL-1beta expression are measured. Given that many researchers are not molecular biologists by training, yet need an appreciation of the controls that regulate the function of key proteins such as IL-1beta, this review is aimed at both: (a) clarifying the multiple levels at which IL-1beta production is modulated and (b) using IL-1beta regulation to explain the dynamics of gene regulation to non-molecular biologists. Three major topics will be discussed. First, regulation of IL-1beta production will be examined at every level from extracellular signals that trigger gene activation through release of active protein into the extracellular fluid. Second, regulation of IL-1beta bioavailability and bioactivity will be discussed. This section examines the fact that even after IL-1beta is released, it may or may not be able to exert a biological action due to multiple modulatory factors. Last is the introduction of the idea that IL-1beta regulation is, at times, beyond the direct control of host; that is, when IL-1beta production becomes dysregulated by pathogens.