Interleukin-1β
| Interleukin-1β | ||
|---|---|---|
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| Interleukin 1 beta monomeric, human | ||
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Existing structural data: s. UniProt |
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| Properties of human protein | ||
| Mass / length primary structure | 153 amino acids | |
| Secondary to quaternary structure | Monomer | |
| Identifier | ||
| Gene name | IL1B | |
| External IDs | ||
| Occurrence | ||
| Homology family | IL1B | |
| Parent taxon | Euteleostomi | |
Interleukin-1β (or IL-1β or IL-1B for short ) belongs to the interleukin-1 family and is one of the cytokines that are counted among the inflammation mediators . It is mainly produced by blood monocytes and is a central messenger substance in the host organism's response to a number of external influences (such as lipopolysaccharides as exogenous pyrogens ). Interleukin-1β was particularly researched by Charles Dinarello .
Genetics, transcription, secretion
IL-1β is encoded on chromosome segment 2q14 with 810 base pairs and initially transcribed as an inactive interleukin-1β precursor protein with 266 amino acids and a molecular mass of 30.75 kDa. The synthesis is stimulated by toll-like receptor agonists. Most of the IL-1β precursor proteins are then found in the cytosol , but some migrate to special secretory lysosomes . This is where the IL-1β precursor comes together with procaspase-1. The active caspase-1 has to be split off from this, which then separates from the IL-1β precursor protein the 153 amino acid strong active interleukin-1β, which is secreted (closely related to this event).
This step of activation and secretion of the IL-1β from its precursor protein appears to be a tightly regulated step. One possibility is the activation of IL-1β mediated by intracellular calcium. The stimulation of the P2X7 receptor by extracellular ATP leads to an influence of calcium ions in the cell, which activates phospholipases. It appears that calcium-independent phospholipase A2 is necessary for caspase-1 activation in the lysosomes, while phosphatidylcholine-specific phospholipase C is necessary for exocytosis and secretion of IL-1β from the lysosomes . Caspase-1 can also be activated by the inflammasome , a protein complex in the cytosol of macrophages and neutrophils that is activated by bacterial components or, in the case of a gout attack , by uric acid crystals (simplified representation of this area, which is still under research).
In circulating monocytes and bone marrow macrophages from healthy individuals, gene expression of the IL1β precursor cannot be detected. If these cells are stimulated by lipopolysaccharides from bacterial walls or other (also endogenous) pyrogens, then it increases sharply. But not all precursor IL-1β also appear as active IL-1β in the blood (despite the constitutionally present procaspase-1 in cells), since activation and secretion are regulated. Dysregulation at any level of activation and secretion of interleukin-1β can trigger IL-1 mediated diseases. In addition to the systemic form of idiopathic juvenile arthritis (Still syndrome), this subheading also includes rare inherited diseases such as B. the familial Mediterranean fever .
Functions
IL-1β is a highly effective cytokine : the injection of just a few nanograms is enough to e.g. B. fever , an increase in neutrophils , platelets , acute phase proteins and circulating interleukin-6 . Since interleukin-1β only occurs in the picomolar range in the blood, a reliable measurement is only possible when it is significantly increased. The production at the cellular level can be demonstrated in cell cultures.
Like interleukin-1α, IL-1β acts on two interleukin-1 receptors:
- The type 1 interleukin-1 receptor (IL-1R1) carries the signals of the IL-1, it is always present on all cells and its expression is hardly regulated. Its activation can, however, be antagonized by the interleukin-1 receptor antagonist (IL1Ra) also formed by the organism ; so it is regulated by the balance between IL-1 and IL-1Ra.
- The interleukin-1 receptor type 2 (IL-1R2) captures the interleukin without transmitting its signals and thus also helps to limit the interleukin-1 effect.
IL-1β triggers the transduction of cyclooxygenase-2 via the activated interleukin-1 receptor type 1 in endothelial cells (via NF-κB ) and thus leads to an increased formation of prostaglandin E 2 .
IL-1β is a stimulator of the neurons that release corticotropin-releasing hormones in the hypothalamus and leads to a stimulation of ACTH and the release of cortisone in the adrenal glands during inflammatory reactions.
IL-1β induces the formation of CD14 .
IL-1β triggers interleukin-6 release.
In the bone marrow , it causes an increased release of neutrophils .
Web links
Individual evidence
- ↑ a b Dinarello, CA (2005): Blocking IL-1 in systemic inflammation. J Exp Med 201: 1355-9.
- ↑ a b c Rivest S et al. (2000): How the Blood Talks to the Brain Parenchyma and the Paraventricular Nucleus of the Hypothalamus During Systemic Inflammatory and Infectious Stimuli. Proc Soc Exp Biol Med 223 (1): 22-38.
