Introduction
Overview of the IL-1 Receptor Signaling Pathway
IL-1 is a cytokine produced by activated macrophages which mediates several physiological responses to infections and injuries, including stimulation of thymocyte proliferation, B-lymphocyte maturation and proliferation, induction of acute-phase protein synthesis by hepatocytes and induction of fever. In addition to macrophages, fibroblast keratinocytes, comeal cell astrocytes, and EBV-transformed B-lymphocytes are also capable of producing IL-1. Monocyte cell lines produce IL-1 after treatment with agents such as TPA and LPS.
There are 11 members of the IL-1 family (IL-1F) of ligands including IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra), etc. The main function of IL-1-type cytokines is to control proinflammatory reactions in response to tissue injury by pathogen-associated molecular patterns (PAMPs, such as bacterial or viral products) or damage- or danger-associated molecular patterns released from damaged cells (DAMPs, such as uric acid crystals or adenosine 5´-triphosphate). Thus, they are major mediators of innate immune reactions, and their actions are tightly balanced. The occurrence of severe multiorgan inflammation in patients with homozygous mutations or deletions of the gene encoding interleukin-1 receptor antagonist (IL-1RA) and the successful blockade of inflammatory reactions in humans by application of recombinant IL-1RA or antibodies to IL-1β have demonstrated a central role of IL-1α or IL-1β in a number of auto-inflammatory diseases. This pathway summarizes signaling of the founding members, IL-1α and IL-1β, which share only 24% amino acid sequence identity but have largely identical biological function.
IL-1 is a cytokine produced by activated macrophages which mediates several physiological responses to infections and injuries, including stimulation of thymocyte proliferation, B-lymphocyte maturation and proliferation, induction of acute-phase protein synthesis by hepatocytes and induction of fever. In addition to macrophages, fibroblast keratinocytes, comeal cell astrocytes, and EBV-transformed B-lymphocytes are also capable of producing IL-1. Monocyte cell lines produce IL-1 after treatment with agents such as TPA and LPS.
There are 11 members of the IL-1 family (IL-1F) of ligands including IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra), etc. The main function of IL-1-type cytokines is to control proinflammatory reactions in response to tissue injury by pathogen-associated molecular patterns (PAMPs, such as bacterial or viral products) or damage- or danger-associated molecular patterns released from damaged cells (DAMPs, such as uric acid crystals or adenosine 5´-triphosphate). Thus, they are major mediators of innate immune reactions, and their actions are tightly balanced. The occurrence of severe multiorgan inflammation in patients with homozygous mutations or deletions of the gene encoding interleukin-1 receptor antagonist (IL-1RA) and the successful blockade of inflammatory reactions in humans by application of recombinant IL-1RA or antibodies to IL-1β have demonstrated a central role of IL-1α or IL-1β in a number of auto-inflammatory diseases. This pathway summarizes signaling of the founding members, IL-1α and IL-1β, which share only 24% amino acid sequence identity but have largely identical biological function.
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