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S100a8 serves an important role in cell differentiation and is abnormally expressed in common tumors, but there are few studies on the association between S100a8 and brain I/R injury. The present study aimed to investigate the role of S100a8 in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced BV2 microglia cell injury, and to elucidate the potential underlying molecular mechanisms. BV2 cells were exposed to OGD/R to mimic ischemia/reperfusion (I/R) injury in vitro. S100a8 expression was detected via reverse transcription-quantitative PCR and western blot analyses. Following transfection with short hairpin RNAs targeting S100a8, the levels of inflammatory cytokines and oxidative stress-related factors were determined using commercial kits. Apoptosis was assessed using flow cytometric analysis and the expression levels of apoptosis-related proteins were determined using western blot analysis. Subsequently, the mRNA and protein levels of Grb2-associated binder 1 (GAB1) were assessed following S100a8 silencing. Immunoprecipitation (IP) was performed to verify the association between S100a8 and GAB1. The levels of inflammation, oxidative stress and apoptosis were assessed following GAB1 silencing, along with S100a8 silencing in BV2 cells subjected to OGD/R. The results indicated that exposure to OGD/R markedly upregulated S100a8 expression in BV2 cells. S100a8 silencing inhibited inflammation, oxidative stress and apoptosis, accompanied by changes in the expression of related proteins. The IP assay revealed a strong interaction between GAB1 and S100a8. In addition, GAB1 silencing reversed the inhibitory effects of S100a8 silencing on inflammation, oxidative stress and apoptosis in OGD/R-stimulated BV2 cells. Taken together, the results of the present study demonstrated that S100a8 silencing alleviated inflammation, oxidative stress and the apoptosis of BV2 cells induced by OGD/R, partly by upregulating the expression of GAB1. Thus, these findings may potentially provide a novel direction to develop therapeutic strategies for cerebral I/R injury.

Sepsis is a life-threatening condition in which an uncontrolled inflammatory host response is triggered. The exact pathogenesis of sepsis remains unclear. The aim of the present study was to identify key genes that may aid in the diagnosis and treatment of sepsis. mRNA expression data from blood samples taken from patients with sepsis and healthy individuals was downloaded from the Gene Expression Omnibus database and differentially expressed genes (DEGs) between the two groups were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network construction, was performed to investigate the function of the identified DEGs. Furthermore, for validation of these results, the expression levels of several DEGs were analyzed by reverse transcription quantitative-polymerase chain reaction (RT-qPCR) in three patients with sepsis and three healthy blood samples to support the results obtained from the bioinformatics analysis. Receiver operating characteristic analyses were also used to analyze the diagnostic ability of the identified DEGs for sepsis. The results demonstrated that a total of 4,402 DEGs, including 1,960 upregulated and 2,442 downregulated genes, were identified between patients with sepsis and healthy individuals. KEGG pathway analysis revealed that 39 DEGs were significantly enriched in toll-like receptor signaling pathways. The top 20 upregulated and downregulated DEGs were used to construct the PPI network. Hub genes with high degrees, including interleukin 1 receptor-associated kinase 3 (IRAK3), S100 calcium-binding protein (S100)A8, angiotensin II receptor-associated protein (AGTRAP) and S100A9, were demonstrated to be associated sepsis. Furthermore, RT-qPCR results demonstrated that IRAK3, adrenomedullin (ADM), arachidonate 5-lipoxygenase (ALOX5), matrix metallopeptidase 9 (MMP9) and S100A8 were significantly upregulated, while ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) was upregulated but not significantly, in blood samples from patients with sepsis compared with healthy individuals, which was consistent with bioinformatics analysis results. Therefore, AGTRAP, IRAK3, ADM, ALOX5, MMP9, S100A8 and ENTPD1 were identified to have potential diagnostic value in sepsis. In conclusion, dysregulated levels of the AGTRAP, IRAK3, ADM, ALOX5, MMP9, S100A8 and ENTPD1 genes may be involved in sepsis pathophysiology and may be utilized as potential diagnostic biomarkers or therapeutic targets.

Calprotectin in mucosal epidermal keratinocytes has an important role in fighting microbial infections. S100A8 belongs to the S100 protein family and is a subunit of calprotectin (heterodimer complex of S100A8/A9). Interleukin‑1α (IL‑1α) is one of the cytokines produced by oral keratinocytes. The primary aims of the present study were to investigate the effect of IL‑1α on the expression of S100A8 and its underlying molecular mechanism in oral epithelial cells. Determining the molecular mechanism of the induced expression of S100A8 by IL‑1α aims to improve current understanding of the roles of calprotectin during the infection of mucosal epithelial cells. The expression analysis indicated that IL‑1α significantly induced the expression of S100A8 in human TR146 epithelial cells at the mRNA and protein levels, respectively. The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region (‑165/‑111). The results of electrophoresis mobility shift assay and chromatin immunoprecipitation assay also demonstrated that the CCAAT/enhancer binding protein β (C/EBPβ) binding site (‑113/‑109) in the S100A8 promoter region was involved into the upregulatory effect on the expression of S100A8 induced by IL‑1α. Taken together, these results suggested that the activation of the expression of S100A8 induced by IL‑1α in TR146 epithelial cells involves a mechanism by which the binding activity of C/EBPβ to the specific site (‑113/‑109) of the S100A8 promoter is increased.