Molecular immunology
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Molecular immunology · Jan 2019
Clinical TrialEvaluation of Epstein-Barr virus-specific antibodies in Cypriot multiple sclerosis patients.
Multiple Sclerosis (MS) is a chronic, demyelinating, inflammatory disease of the central nervous system (CNS) with a strong autoimmune component. Several genetic and environmental factors have been suggested to contribute in MS. The Epstein-Barr virus (EBV) is one pathogenic candidate proposed to be involved in the onset of MS and/or induction of subsequent exacerbations. ⋯ There was no significant difference in the presence/absence of EA-D IgG between the two groups nor in the corresponding P. I. levels. The results obtained, revealing higher seropositivity of EBNA-1 IgG and VCA IgG in MS patients, seem to concur with previous findings of studies in other countries, thereby further asserting the theory of EBV involvement in MS.
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Molecular immunology · Nov 2018
microRNA-199a may be involved in the pathogenesis of lupus nephritis via modulating the activation of NF-κB by targeting Klotho.
Klotho is considered to have renal protective effect by prohibiting the activation of the nuclear factor (NF)-κB pathway, while the role of microRNA-199a (miR-199a)/Klotho in lupus nephritis (LN) is still unknown. A single dose of pristane (0.5 ml) was intraperitoneally injected into 8 weeks-old female mice to establish the LN model. MiR-199a mimic or miR-199a inhibitor, Klotho plasmid or Klotho siRNA, and miR-199a inhibitor plus si-Klotho were transfected into lipopolysaccharides (LPS) stimulated human embryonic kidney 293 T (HEK293 T) cells. ⋯ MiR-199a promoted LPS-induced NF-κB activation and improved the secretion of TNF-α and IL-1β by regulation of Klotho in HEK293 T cells. If miR-199a antagomir was administrated after 48 h of pristane administration, the expression of p-P65 and the secretion of TNF-α and IL-1β were significantly down-regulated in LN kidney. Although the direct involvement and detailed mechanism of miR-199a in LN still need further investigation, our data show that MiR-199a could regulate the activation of NF-κB by directly targeting Klotho.
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Molecular immunology · Oct 2018
ReviewRole of complement C5a and histones in septic cardiomyopathy.
Polymicrobial sepsis (after cecal ligation and puncture, CLP) causes robust complement activation with release of C5a. Many adverse events develop thereafter and will be discussed in this review article. Activation of complement system results in generation of C5a which interacts with its receptors (C5aR1, C5aR2). ⋯ There is also evidence that CLP causes release of IL-1β via activation of the NLRP3 inflammasome in CMs of septic hearts or in CMs incubated in vitro with C5a. Many of these events occur after in vivo or in vitro contact of CMs with histones. Together, these data emphasize the role of complement (C5a) and C5a receptors (C5aR1, C5aR2), as well as extracellular histones in events that lead to cardiac dysfunction of sepsis (septic cardiomyopathy).
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Molecular immunology · Sep 2018
An integrated deep sequencing analysis of microRNAs in transplanted corneas.
Illumina Hiseq 2500 deep sequencing was used to screen for differentially expressed genes (DEGs) in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Our results showed that 22 miRNAs were significantly upregulated and 4 were significantly downregulated in the isograft group when compared with the control group (P < 0.01), while 17 miRNAs were significantly upregulated and 3 were significantly downregulated in the allograft group when compared with the isograft group (P < 0.01). Among the miRNAs with altered expression levels, miR-155-5p, miR-142-3p, miR-142-5p, and miR-223-3p displayed simultaneous changes in the above two comparisons. ⋯ Furthermore, the MetaCore analysis identified C/EBP beta, p53, and sp1 as key transcription factors in that network. Our study identified transplanted corneas-specific miRNA in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Furthermore, bioinformatics analysis of the key miRNA regulatory network revealed the molecular mechanisms, which suggests miRNAs may as new molecular targets for treating corneal injuries and corneal transplant rejection.
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Molecular immunology · Sep 2018
Inhibition of ER stress-related IRE1α/CREB/NLRP1 pathway promotes the apoptosis of human chronic myelogenous leukemia cell.
Endoplasmic reticulum (ER) stress is induced in chronic myelogenous leukemia (CML) cells. As an important sensor of ER stress, inositol-requiring protein-1α (IRE1α) promotes the survival of acute myeloid leukemia. NLRP1 inflammasome activation promotes metastatic melanoma growth and that IRE1α can increase NLRP1 inflammasome gene expression. ⋯ Downregulation of IRE1α or NLRP1 suppressed the proliferation and elevated the apoptosis of primary CML cells. Collectively, this study demonstrated that the IRE1α/CREB/NLRP1 pathway contributes to the progression of CML and the development of imatinib resistance. Hence, targeting ER stress-related IRE1α expression or NLRP1 inflammasome activation may block CML development.