Ischemic stroke after cerebral artery occlusion is one of the major causes of chronic disability worldwide. Interleukins (ILs) play a bidirectional role in ischemic stroke through information transmission, activation and regulation of immune cells, mediating the activation, multiplication and differentiation of T and B cells and in the inflammatory reaction. Crosstalk between different ILs in different immune cells also impact the outcome of ischemic stroke. This overview is aimed to roughly discuss the multiple roles of ILs after ischemic stroke. The roles of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-19, IL-21, IL-22, IL-23, IL-32, IL-33, IL-34, IL-37, and IL-38 in ischemic stroke were discussed in this review.

BackgroundInflammatory responses play a multiphase role in the pathogenesis of cerebral ischemic stroke (IS). Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, reduces inflammatory responses via the JAK2/STAT3 pathway. Based on its anti-inflammatory and immunosuppressive effects, we hypothesized that it may have a protective effect against stroke. The aim of this study was to investigate whether inhibition of JAK2 has a neuroprotective effect on ischemic stroke and to explore the potential molecular mechanisms.MethodsRux, MCC950 or vehicle was applied to middle cerebral artery occlusion (MCAO) mice in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. After 3 days of reperfusion, neurological deficit scores, infarct volume and brain water content were assessed. Immunofluorescence staining and western blots were used to measure the expression of NLRP3 inflammasome components. The infiltrating cells were investigated by flow cytometry. Proinflammatory cytokines were assessed by RT-qPCR. The expression of the JAK2/STAT3 pathway was measured by western blots. Local STAT3 deficiency in brain tissue was established with a lentiviral vector carrying STAT3 shRNA, and chromatin immunoprecipitation (ChIP) assays were used to investigate the interplay between NLRP3 and STAT3 signaling.ResultsRux treatment improved neurological scores, decreased the infarct size and ameliorated cerebral edema 3 days after stroke. In addition, immunofluorescence staining and western blots showed that Rux application inhibited the expression of proteins related to the NLRP3 inflammasome and phosphorylated STAT3 (P-STAT3) in neurons and microglia/macrophages. Furthermore, Rux administration inhibited the expression of proinflammatory cytokines, including TNF-α, IFN-γ, HMGB1, IL-1β, IL-2, and IL-6, suggesting that Rux may alleviate IS injury by inhibiting proinflammatory reactions via JAK2/STAT3 signaling pathway regulation. Infiltrating macrophages, B, T, cells were also reduced by Rux. Local STAT3 deficiency in brain tissue decreased histone H3 and H4 acetylation on the NLRP3 promoter and NLRP3 inflammasome component expression, indicating that the NLRP3 inflammasome may be directly regulated by STAT3 signaling. Rux application suppressed lipopolysaccharide (LPS)-induced NLRP3 inflammasome secretion and JAK2/STAT3 pathway activation in the OGD/R model in vitro.ConclusionJAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting the expression of downstream proinflammatory cytokines and the acetylation of histones H3 and H4 on the NLRP3 promoter, resulting in the downregulation of NLRP3 inflammasome expression.

Stroke is the leading cause of disability and mortality in the world, but the pathogenesis of ischemic stroke (IS) is not completely clear and treatments are limited. Mounting evidence indicate that neovascularization is a critical defensive reaction to hypoxia that modulates the process of long-term neurologic recovery after IS. Angiogenesis is a complex process in which the original endothelial cells in blood vessels are differentiated, proliferated, migrated, and finally remolded into new blood vessels. Many immune cells and cytokines, as well as growth factors, are directly or indirectly involved in the regulation of angiogenesis. Inflammatory cells can affect endothelial cell proliferation, migration, and activation by secreting a variety of cytokines via various inflammation-relative signaling pathways and thus participate in the process of angiogenesis. However, the mechanism of inflammation-mediated angiogenesis has not been fully elucidated. Hence, this review aimed to discuss the mechanism of inflammation-mediated angiogenesis in IS and to provide new ideas for clinical treatment of IS.

TUBA1C, a microtubule component, contributes to the development of several cancers. Our purpose was to study the expression of TUBA1C, its potential prognostic value, and its effects on the infiltration of immune cells of low-grade glioma (LGG). Through applying multiple bioinformatics analyses, we extracted and analyzed datasets from TCGA, TIMER, GTEx, GEPIA, and HPA to investigate the potential oncogenic mechanisms of TUBA1C, including the correlation between TUBA1C and prognosis, immune-checkpoints, tumor microenvironment (TME), and infiltration of immune cells in LGG. GO functional annotations and KEGG pathway analyses were further applied to investigate the potential action of TUBA1C in LGG. We revealed that the mRNA levels of TUBA1C were increased in LGG tumor tissues than in normal tissues. Additionally, TUBA1C was up-regulated in the grade III of LGG than in grade II. Moreover, we found that TUBA1C may be an independent prognostic factor of LGG, and high TUBA1C expression correlated to a poor prognosis of LGG. TUBA1C expression was positively associated with the infiltration of B cells, CD8 T+ cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils. TUBA1C was also verified to be co-expressed with immune-related genes and immune-checkpoints. GO and KEGG pathway analyses indicated that TUBA1C may potentially regulate the pathogenesis of LGG through immune-related pathways, including chemokine pathway; JAK-STAT pathway; natural killer cell mediated cytotoxicity; T cell receptor pathway; leukocyte migration; negative regulation of immune system process; regulation of lymphocyte activation; T cell activation and other pathways. In conclusion, TUBA1C expression is increased in LGG and high TUAB1C expression is related to a poor prognosis. TUBA1C may influence tumor development by regulating the tumor-infiltrating cells in the TME. TUBA1C may be a potential target for immunotherapy.

Background Anti‐silencing function 1 (ASF1) is a conserved histone H3–H4 chaperone protein. ASF1B, a paralog of ASF1, acts by promoting cell proliferation and influencing cell cycle progression. Although there is some evidence demonstrating that ASF1B plays a key role in the development, progression, and prognosis of certain cancers, there are no pan‐cancer analyses of ASF1B. Methods We used a range of bioinformatics approaches to investigate the predictive role of ASF1B, including its correlation with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), and immune cell infiltration, in diverse cancer types. Results We found that ASF1B was highly expressed in 22 cancers and was negatively correlated with the prognosis of multiple major cancer types. Furthermore, ASF1B expression was correlated with TMB in 21 cancers and with MSI in 7 cancers. We found that ASF1B was coexpressed with genes encoding immune activators, immune suppressors, major histocompatibility complexes, chemokines, and chemokine receptors. We further found that the role of ASF1B in the infiltration of different types of immune cells varied across tumor types. ASF1B may potentially affect several key immune‐related pathways, such as those involved in antigen processing and presentation, natural killer cell‐mediated cytotoxicity, and autoimmune thyroid disease. Conclusions Our findings show that ASF1B may serve as a prognostic marker and potential immunotherapeutic target for several malignancies due to its role in tumorigenesis and immune infiltration.