Human albumin attenuates excessive innate immunity via inhibition of microglial Mincle/Syk signaling in subarachnoid hemorrhage

Preliminary exploration of the potential of spliceosome‐associated protein 130 for predicting disease severity in Crohn's disease

“…SAP130 activates Mincle signaling in neurons, resulting in increased expression of the inflammatory cytokine TNF, which is associated with deleterious outcomes. Binding of SAP130 to its receptor Mincle initiates the Mincle/Syk/IL‐1β signaling pathway to induce elevated expression of molecules/proteins associated with inflammation (iNOS, IL‐1b, CD11b, CD16, CD32, and NLRP3) and chemokines (CXCL‐1 and CXCL‐2), which mediates the cross talk between neuronal necroptosis and microglial sterile inflammation response during subarachnoid hemorrhage . A mouse model of subarachnoid hemorrhage induced by endovascular perforation showed similar results, and these effects eventually lead to blood–brain barrier disruption and neuronal dysfunction.…”

“…SAP130 was recently demonstrated to be a novel and promising marker for nonpathogen‐mediated hepatitis and neuroinflammation . Normally, it is located in the nucleus in live cells, but it is released into the extracellular milieu to mediate inflammation response during cellular stress or cell death.…”

“…SAP130 was recently demonstrated to be a novel and promising marker for nonpathogen-mediated hepatitis and neuroinflammation. [14][15][16][17][18][19] Normally, it is located in the nucleus in live cells, but it is released into the extracellular milieu to mediate inflammation response during cellular stress or cell death. de Rivero et al 19 have identified increased expression of SAP130 and Mincle in cortical neurons after traumatic brain injury in both humans and rodents.…”

“…It specifically binds to the Mincle (macrophage‐inducible C‐type lectin, CLEC4E) receptor, which is a transmembrane PRR expressed on innate immune cells, including macrophages, dendritic cells, and neutrophils, and initiates the Fc receptor common γ‐chain (FcRγ)–spleen tyrosine kinase (Syk) signaling axis to transduce downstream signals, resulting in a potent inflammatory response . Studies have shown that apparent SAP130 release is associated with acute or chronic hepatitis, such as concanavalin A hepatitis and alcohol‐induced liver injury, and neuroinflammation, such as subarachnoid hemorrhage and traumatic brain injury . Consequently, this suggests that SAP130 might act as an alarmin for excessive cell death and be involved in innate immune response under conditions of sterile inflammation.…”

“…[11][12][13] Studies have shown that apparent SAP130 release is associated with acute or chronic hepatitis, such as concanavalin A hepatitis and alcohol-induced liver injury, [14][15][16] and neuroinflammation, such as subarachnoid hemorrhage and traumatic brain injury. [17][18][19] Consequently, this suggests that SAP130 might act as an alarmin for excessive cell death and be involved in innate immune response under conditions of sterile inflammation.…”