Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Macrophages play important roles in the inflammatory process of sepsis by secreting chemokines. Chemokine (CC-motif) ligand 2 (CCL-2) is one of the main proinflammatory chemokines secreted by macrophages that plays a critical role in the recruitment of more monocytes and macrophages to the sites of injury in sepsis, but the mechanisms that regulate CCL-2 expression in macrophages during sepsis are still unknown. ⋯ We further confirmed miR-155 regulated SGK3 to increase LPS-induced CCL-2 by using miR-155 mimics and SGK3 overexpression. Thus, our study demonstrates that miR-155 targets SGK3 to increase LPS-induced CCL-2 expression in macrophages, which promotes macrophage chemotaxis and enhances organs injury during endotoxemia. Our study contributed to a better understanding of the mechanisms underlying the inflammatory response during sepsis.
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Hemorrhagic shock (HS) is accompanied by a pronounced activation of the inflammatory response in which acute lung injury (ALI) is one of the most frequent consequences. Among the pivotal orchestrators of this inflammatory cascade, extracellular cold-inducible RNA-binding protein (eCIRP) emerges as a noteworthy focal point, rendering it as a promising target for the management of inflammation and tissue injury. Recently, we have reported that oligonucleotide poly(A) mRNA mimic termed A 12 selectively binds to the RNA binding region of eCIRP and inhibits eCIRP binding to its receptor TLR4. ⋯ A 12 treatment also decreased lung levels of TNF-α, MIP-2, and KC mRNA expressions. Lung histological injury score, neutrophil infiltration (Ly6G staining and myeloperoxidase activity), and lung apoptosis were significantly attenuated after A 12 treatment. Our study suggests that the capacity of A 12 in attenuating HS-induced ALI and may provide novel perspectives in developing efficacious pharmaceutics for improving hemorrhage prognosis.