Interleukin-1 receptor type 2 (IL-1R2) functions as a decoy receptor that suppresses IL-1-induced inflammatory signaling. Both membrane-bound IL-1R2 (WT IL-1R2) and its soluble form (sIL-1R2) bind interleukin-1α (IL-1α) at the cell surface or in the extracellular space, thereby inhibiting downstream signaling. However, the anti-inflammatory role of IL-1R2 varies depending on the cellular context and receptor structure. In this study, we generated two IL-1R2 deletion mutants—ΔTM, lacking the transmembrane domain, and ΔTMCP, lacking both the transmembrane and cytoplasmic domains—and compared their functions with those of WT IL-1R2 in HeLa cells. Western blotting, immunoprecipitation, and enzyme-linked immunosorbent assay were used to assess receptor expression, IL-1α binding, and IL-1β-induced interleukin-8 (IL-8) production, respectively. Both ΔTM and ΔTMCP were secreted more efficiently than WT IL-1R2. WT IL-1R2 exhibited weak intracellular interaction with IL-1α, whereas the deletion mutants showed minimal binding. WT IL-1R2 most effectively suppressed IL-1α extracellular release; however, ΔTM and ΔTMCP also reduced secretion. Notably, both deletion mutants suppressed IL-1β-induced IL-8 production more effectively than WT IL-1R2, indicating enhanced extracellular decoy activity. These findings demonstrate that structural modifications of IL-1R2 influence its function as a decoy receptor, and the enhanced inhibitory effects of the deletion mutants on IL-1 signaling provide new insight into the anti-inflammatory potential of soluble IL-1R2 in non-immune cells.

Key words: Interleukin-1, Interleukin-1 receptor type 2, decoy receptor, transmembrane, soluble interleukin-1 receptor type 2

S100A11 is a small calcium-binding protein that has been studied in the context of growth regulation and membrane repair. However, it has recently been linked to the disassembly of focal adhesions. This new role of S100A11 has been linked to calcium influx through the stretch-activated channel Piezo1. In this review, we look at what’s currently known about S100A11’s structural features, interactome, and functional roles. We focus on how it responds to mechanical stress and becomes recruited to focal adhesions. We also look into its role in the disassembly of these adhesions and consider potential mechanisms. To place its activity in context, we compare S100A11 with other members of the S100 family members and discuss its contribution to calcium-dependent cytoskeletal regulation and extracellular signaling. We examine the effects of S100A11 activity in cancer metastasis, wound healing, and fibrosis. Finally, we evaluate potential ways to modulate S100A11 function for prospective therapeutic intervention. Collectively, this review projects S100A11 as a mechanosensitive calcium effector at the intersection of adhesion biology and mechanotransduction.

Key words: S100A11, focal adhesions, mechanosensing, Piezo1, cytoskeleton, cell migration, cancer