Interleukin-36 alpha (IL-36α), also known as IL-1F6, is a member of the interleukin-1 (IL-1) cytokine family. This family includes several pro-inflammatory cytokines that play crucial roles in the regulation of immune responses. IL-36α is particularly significant due to its involvement in both innate and adaptive immunity.
IL-36α is a 160 amino acid protein that lacks a signal sequence, prosegment, and potential N-linked glycosylation sites . It is produced by various cells, including epithelial and immune cells, and is released in response to stimuli such as lipopolysaccharides (LPS) and ATP-induced activation of the P2X7 receptor . The protein is expressed and purified from E. coli for recombinant use .
IL-36α functions by binding to its receptor, IL-36R, which then recruits the accessory protein IL-1RAcP to form a ternary complex . This complex activates intracellular signaling pathways, including NF-κB and MAPK, leading to the production of pro-inflammatory mediators . The activation of these pathways is crucial for the cytokine’s role in immune responses.
IL-36α plays a significant role in the inflammatory response. It is involved in the activation of MAPK and NF-κB pathways, which are essential for the production of inflammatory cytokines and chemokines . This cytokine is also implicated in the pathophysiology of several diseases, including psoriasis and other inflammatory conditions .
Dysregulation of IL-36α signaling can lead to various inflammatory diseases. For instance, in the skin, IL-36α contributes to host defense through inflammatory responses. However, when dysregulated, it can stimulate keratinocytes and immune cells, enhancing the Th17/Th23 axis and inducing psoriatic-like skin disorders . Genetic mutations in the antagonist IL-36Ra are associated with generalized pustular psoriasis, a severe skin disease .
Recombinant mouse IL-36α is produced for research purposes to study its biological functions and potential therapeutic applications. The recombinant protein is typically lyophilized and can be reconstituted for use in various experimental setups . It is essential to store the protein under sterile conditions at -20°C to -80°C to maintain its stability and avoid repeated freeze-thaw cycles .