Overview of IL-1α signaling pathway. The binding of IL-1α to IL-1RI leads to dimerization of the receptor at the TIR domain and recruitment of IL-1RAcP. This IL-1α/IL-1RI/IL-1RAcP complex then recruits adaptor proteins MyD88 and IRAK for subsequent downstream signaling cascade. IRAK will phosphorylate IRAK1 and IRAK2 and recruit TRAF6 to form the IRAK1-IRAK2-TRAF6 complex; subsequently TRAF6 will associate with TAK1-TAB1-TAB2 to phosphorylate TAK1. Phosphorylated TAK1 will dissociate from the TRAF6-TAK1-TAB1-TAB2 complex to initiate the NF-κB and MAPK signaling pathways to regulate the downstream proinflammatory cytokines expressions, such as IL-6, TNF-α and cyclooxygenase 2. Abbreviations: IL-1RI, IL-1 receptor I; IL-1RAcP, interleukin-1 receptor accessory protein; MyD88, myeloid differentiation factor 88; IRAK, IL-1R-associated kinase; TRAF6, tumor necrosis factor–associated factor 6; TAK1, transforming growth factor-β-activated kinase 1; NF- κB, nuclear factor kappa-B; MAPK, Mitogen-activated protein kinase.