Mouse IL-1α Antibody

Interleukin-1 alpha (IL-1α) is a member of the IL-1 family of pro-inflammatory cytokines and plays an important role in the regulation of immune responses. It is constitutively expressed by many cell types, including fibroblasts, keratinocytes, macrophages, dendritic cells and T cells. Although, endothelial and epithelial cells are the main source of IL-1α under physiological and pathological conditions [1].

Both IL-1 group members, IL-1α and IL-1β, are expressed as precursors that are further processed into mature secreted forms. However, unlike IL-1β, the pro-form and the mature version of IL-1α show strong biological activities [2]. The pro-IL-1α can be cleaved by several proteases (e.g. granzyme B, caspase-5 and -11, calpain) into a 17-kDa mature form and a 16-kDa N-terminal 'propiece' harboring a nuclear localization sequence (NLS) [1]. 

Following protease-dependent processing, the mature IL-1α is rapidly secreted through pores of the plasma membrane. There, it interacts with the IL-1 receptor 1 (IL-1R1), which is shared with IL-1β. Upon receptor-ligand binding, a structural change of the receptor occurs allowing the co-receptor IL-1R3 to bind and form a trimeric complex [3]. Subsequently, the intracellular adapter protein MyD88 (myeloid differentiation primary response 88) becomes phosphorylated triggering an intricate sequence of (auto-) phosphorylation, complex formation and ubiquitination events. Finally, activated NK-kB, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways induce the expression of inflammatory cytokines and chemokines, such as IL-6 and IL-8 [4].

Indeed, IL-1α is quite unique as it appears to be the only cytokine that could (a) translocate into the nucleus to regulate downstream gene expressions, (b) anchor to the cell membrane to activate IL-1/IL-1R signaling, (c) secrete out of the cell and activate the IL-1/IL1R signaling, and (d) stay in the cytosol with unknown function. The underlying mechanisms that determine and regulate its subcellular dual-functional localization remain a major question in this field [1].

In response to tissue damage or pathogen invasion, IL-1α is either released from dying cells as an alarmin, or exposed on the surface of cells undergoing oxidative or metabolic stress [2]. Due to its role in mediating acute and local inflammation, IL-1α has emerged as a therapeutic target for diseases characterized by tissue or organ inflammation (e.g. myositis, COVID-19, cancer) [1-2].

References

1. Chiu JW, et al., 2021. IL-1α Processing, Signaling and Its Role in Cancer Progression. Cells. 2021 Jan 7;10(1):92.
2. Dinarello CA, et al.,  2021. Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases. Autoimmunity Reviews, Volume 20, Issue 3.
3. Dinarello CA, et al., 2018. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 281(1): 8–27.
4. Weber A, et al., 2010. Interleukin-1 (IL-1) pathway. Sci Signal. 3(105).