Regulation of Cytokine Gene Expression in Immunity and Diseases

Amir S. Yazdi, Kamran Ghoreschi, Yazdi, Amir S., Ghoreschi, Kamran

Xiaojing Ma

The interleukin-1 (IL-1) family consists of several pro- or anti-inflammatory proteins, with pro-inflammatory IL-1β being its best characterized member. IL-1β is one of the most prominent mediators of inflammation resulting in fever and immune activation via binding to IL-1 receptor 1. Due to its potency, its secretion is tightly regulated. First the transcription of the biologically inactive proform is induced by TLR activation, TNF, or IL-1 receptor activation by mature IL-1α or IL-1β. For the secretion of IL-1β, inflammasome activation as second stimulus is needed. Inflammasomes are cytosolic protein complexes whose activation results in the maturation of inflammatory caspases such as caspase-1. Caspase-1 then cleaves the inactive pro-IL-1β into its mature form which is then being secreted. While IL-1α and IL-1β are considered pro-inflammatory, IL-1Ra as a naturally occurring receptor antagonist acts as an inhibitor on IL-1 receptor signaling. Further members of the IL-1 family, such as IL-18, IL-33, or IL-36, are even involved in T-helper-cell differentiation and will also be discussed in this chapter.