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Expression of S100 family proteins in neonatal rats with sepsis and its significance.

ABSTRACT: This study aims to study the expression changes of S100 family proteins in neonatal rats with sepsis and investigate the effect and significance of S100 family proteins in pathogenesis and development of sepsis.The functions of S100 family proteins were analyzed with bioinformatics. The immune-associated proteins were chosen as the candidate proteins. Twenty neonatal SPF SD rats were randomly divided into two groups: sepsis model group and control group. The liver sample was stained with HE to evaluate the establishment of sepsis model. The expression amount of proinflammatory factor IL-1, IL-6 and TNF-? was detected with ELISA. The expression changes of S100A8, S100A9, S100A11 and S100A12 in sepsis model rats were detected with real-time PCR and Western blotting. After shRNA plasmid was transfected into THP-1 cells and the expression of S100A12 was silenced, the expression changes of proinflammatory factor IL-1, IL-6 and TNF-? in LPS-induced inflammation were studied in order to investigate the S100A12 mediated inflammatory process.IL-1, IL-6 and TNF-? in the serum of rats with sepsis induced by LPS were 55.79 ± 3.80 ng/l, 48.76 ± 1.03 ng/l and 29.98 ± 2.27 ng/l respectively. S100A8, S100A9, S100A11 and S100A12 detected with real-time PCR in sepsis model group were 14.4 ± 1.37, 10.23 ± 1.81, 5.5 ± 1.64 and 9.97 ± 1.82 respectively. Compared with the control group, S100A8, S100A9, and S100A12 were significantly up-regulated. The shRNA silenced the expression of S100A12 which reduced the expression of proinflammatory factors after LPS stimulated the cells (P < 0.05).Compared with the control group, S100A8, S100A9, and S100A12 were significantly up-regulated in rat sepsis model group. After the expression of S100A12 in propylene glycol monomethyl ether acetate (PMA) induced human macrophages was silenced, the expression of proinflammatory factor IL-1, IL-6 and TNF-? was down-regulated.

SUBMITTER: Huang H

PROVIDER: S-EPMC4396268 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Expression of S100 family proteins in neonatal rats with sepsis and its significance.

Huang Haiying H Tu Luoyang L

International journal of clinical and experimental pathology 20150201 2

<h4>Objective</h4>This study aims to study the expression changes of S100 family proteins in neonatal rats with sepsis and investigate the effect and significance of S100 family proteins in pathogenesis and development of sepsis.<h4>Methods</h4>The functions of S100 family proteins were analyzed with bioinformatics. The immune-associated proteins were chosen as the candidate proteins. Twenty neonatal SPF SD rats were randomly divided into two groups: sepsis model group and control group. The liv ...[more]

PMID: 25973048

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Project description:Sepsis is a leading cause of perinatal mortality worldwide. Breast milk (BM) feeding is protective against neonatal sepsis, but the molecular mechanisms remain unexplained. Despite various supplementations with potential bioactive components from BM formula feeding cannot protect from sepsis. S100-alarmins are important immunoregulators in newborns preventing excessive inflammation. At high concentrations, the S100A8/A9 protein complex also has antimicrobial properties due to its metal ion chelation capacity. To assess whether BM contains S100-alarmins that might mediate the sepsis-protective effect of BM 97 human BM samples stratified for gestational age, mode of delivery and sampling after birth were collected and analyzed. S100A8/A9 levels were massively elevated after birth (p?<?0.0005). They slowly decreased during the first month of life, then reaching levels comparable to normal values in adult serum. The concentration of S100A8/A9 in BM was significantly higher after term compared with preterm birth (extremely preterm, p?<?0.005; moderate preterm, p?<?0.05) and after vaginal delivery compared with cesarean section (p?<?0.0005). In newborn s100a9-/- mice, enterally supplied S100-alarmins could be retrieved systemically in the plasma. To explore the antimicrobial activity against common causal pathogens of neonatal sepsis, purified S100-alarmins and unmodified as well as S100A8/A9-depleted BM were used in growth inhibition tests. The high amount of S100A8/A9 proved to be an important mediator of the antimicrobial activity of BM, especially inhibiting the growth of manganese (Mn) sensitive bacteria such as Staphylococcus aureus (p?<?0.00005) and group B streptococci (p?<?0.005). Depletion of S100A8/A9 significantly reduced this effect (p?<?0.05, respectively). The growth of Escherichia coli was also inhibited by BM (p?<?0.00005) as well as by S100A8/A9 in culture assays (p?<?0.05). But its growth in BM remained unaffected by the removal of S100A8/A9 and was neither dependent on Mn suggesting that the antimicrobial effects of S100A8/A9 in BM are primarily mediated by its Mn chelating capacity. In summary, the enteral supply of bioavailable, antimicrobially active amounts of S100-alarmins might be a promising option to protect newborns at high risk from infections and sepsis.

Project description:BackgroundAmong the EF-Hand calcium-binding proteins the subgroup of S100 proteins constitute a large family with numerous and diverse functions in calcium-mediated signaling. The evolutionary origin of this family is still uncertain and most studies have examined mammalian family members.ResultsWe have performed an extensive search in several teleost genomes to establish the s100 gene family in fish. We report that the teleost S100 repertoire comprises fourteen different subfamilies which show remarkable similarity across six divergent teleost species. Individual species feature distinctive subsets of thirteen to fourteen genes that result from local gene duplications and gene losses. Eight of the fourteen S100 subfamilies are unique for teleosts, while six are shared with mammalian species and three of those even with cartilaginous fish. Several S100 family members are found in jawless fish already, but none of them are clear orthologs of cartilaginous or bony fish s100 genes. All teleost s100 genes show the expected structural features and are subject to strong negative selection. Many aspects of the genomic arrangement and location of mammalian s100 genes are retained in the teleost s100 gene family, including a completely conserved intron/exon border between the two EF hands. Zebrafish s100 genes exhibit highly specific and characteristic expression patterns, showing both redundancy and divergence in their cellular expression. In larval tissue expression is often restricted to specific cell types like keratinocytes, hair cells, ionocytes and olfactory receptor neurons as demonstrated by in situ hybridization.ConclusionThe origin of the S100 family predates at least the segregation of jawed from jawless fish and some extant family members predate the divergence of bony from cartilaginous fish. Despite a complex pattern of gene gains and losses the total repertoire size is remarkably constant between species. On the expression level the teleost S100 proteins can serve as precise markers for several different cell types. At least some of their functions may be related to those of their counterparts in mammals. Accordingly, our findings provide an excellent basis for future studies of the functions and interaction partners of s100 genes and finally their role in diseases, using the zebrafish as a model organism.

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Expression of S100 family proteins in neonatal rats with sepsis and its significance.

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Expression of S100 family proteins in neonatal rats with sepsis and its significance.

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