IL1B

Interleukin- 1β ( IL1B or short ) part of the interleukin -1 family and is one of the many interleukins, which total to cytokines ( mediators of inflammation ) can be counted. It is mainly produced by blood monocytes and is a key chemical messenger in the response of the host organism to a number of external factors (such as lipopolysaccharides as exogenous pyrogens ). Interleukin- 1β was studied in particular by Charles Dinarello.

Genetics, transcription, secretion

IL1β is encoded on chromosome 2q14 section 810 base pairs and initially transcribed as an inactive IL - 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 IL1β precursor proteins then can be found in the cytosol, but a portion goes into specific secretory lysosomes. There, the IL1β precursor comes together with procaspase -1. This must be cleaved active caspase -1, which then by the IL1β precursor protein 153 amino acids, the strong active interleukin- 1β separates which ( closely related to the event ) to be secreted.

Said step of activating the IL1β from its precursor protein and secretion appears to be a tightly regulated step. One possibility is mediated by the activation of intracellular calcium IL1β. Stimulation of the P2X7 receptor by extracellular ATP leads to an influence of calcium ions into the cell which is activated phospholipases. It seems that calcium-independent phospholipase A2 is required for the caspase -1 activation in the lysosomes, while the phosphatidylcholine - specific phospholipase C and secretion of the exocytosis of IL1β is necessary for the lysosomes. Caspase -1 can also be activated by the inflammasome, a protein complex in the cytosol of macrophages and neutrophils, which is activated by bacterial components or, in the case of gout, by uric acid crystals ( highly simplified illustration of this is still under research river basin ).

In circulating monocytes and bone marrow macrophages from healthy individuals gene expression of IL1β precursor is not detectable. When these cells are stimulated by lipopolysaccharides from bacteria or other walls ( endogenous ) pyrogen, then it rises sharply. But not all precursor IL1β also appear as an active IL1β in the blood (despite the constitutionally present in cells procaspase - 1), since just activation and secretion are regulated. Dysregulation at any stage of activation and secretion of interleukin- 1β can induce IL -1 mediated diseases. Here in addition to the systemic form of juvenile idiopathic arthritis ( Still's disease ) are rare inherited disorders such as familial Mediterranean fever.

Functions

IL1β is a potent cytokine: Even the injection less nanograms enough to eg fever to cause an increase in neutrophils, platelets, the acute-phase proteins and circulating interleukin -6. Since IL1β only in Pikomolarbereich living organisms in the blood is concentrated, it can not be measured directly there (this can only be achieved in vitro in cell cultures).

IL1β effect such as interleukin- 1α to two IL-1 receptors:

IL1β triggers on the activated interleukin -1 receptor type 1 in endothelial cells (via NF -kB ), the transduction of cyclooxygenase -2 and also carries an increased formation of prostaglandin E2.

IL1β is a stimulator of neurons which release hormones in the hypothalamic corticotropin releasing and leads over to a stimulation of ACTH and cortisone secretion in the adrenal glands in inflammatory reactions.

IL1β induces the formation of CD14.

IL1β triggers the release of interleukin-6.

In the bone marrow it causes the increased release of neutrophil granulocytes.