IL-1 alpha Protein, Rhesus macaque

The IL-1 alpha protein, a cytokine intrinsically present in almost all quiescent non-hematopoietic cells, plays a pivotal role in inflammation, serving as a crucial link between the innate and adaptive immune systems. Upon binding to its receptor IL1R1, alongside its accessory protein IL1RAP, IL-1 alpha forms the high-affinity interleukin-1 receptor complex, initiating signaling pathways that involve the recruitment of adapter molecules such as MYD88, IRAK1, or IRAK4. This, in turn, activates NF-kappa-B and three MAPK pathways—p38, p42/p44, and JNK pathways. Internally, IL-1 alpha acts as an alarmin, being released into the extracellular space after cell membrane disruption during cell death, thereby inducing inflammation and signaling the host to injury or damage. Beyond its role as a danger signal released during cell necrosis, IL-1 alpha directly senses DNA damage and functions as a signal for genotoxic stress without compromising cell integrity. As a monomer, IL-1 alpha interacts with TMED10, facilitating its translocation from the cytoplasm to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) for secretion. Additionally, it interacts with IL1R1 and S100A13, the latter being the initial step in IL-1 alpha export, followed by the direct translocation of this complex across the plasma membrane.