Sepsis [6,9-13]. Notablly, some of the miRNAs (miRNA

Sepsis
a serious pathological condition of systemic inflammatory response triggered by
body immune system. The stages of infectivity varies form mild to severe,  from systemic inflammatory response sepsis
(SIRS), to severe sepsis, ultimately leading to the last fatal stage,  septic shock. Initial symptoms include fever,
increased heart rate and inflammation followed by organ dysfunction and
multiple organ failure. Approximately 80% of 
the whole genome is altered during the infection leading to generation
of many potential biomarkers. These biomarkers include the C-reactive protein
(CRP), prolactin (PCT), interleukin-6, 
sTERM-1 and miRNAs are released into the blood circulation during the
bacterial and fungal infection 1.
MiRNAs, basically present inside the microvesicle and exosome in order to
protect it from degradation from the RNase and acute pH of the human body 2, 3.
In humans, during the tissue damage or cell apoptosis process, miRNAs are
released into the  blood circulation4. Research investigators have identified a total  17  miRNAs from the blood sample of the  infected sepsis patients which were
differentially expressed such as miRNA-342-5p, miRNA-15a, miRNA-122, miRNA-193,
miRNA-483-5p, miRNA-297, miRNA-181b, miRNA-4661 were downregulated 5-8 while,  miRNA-486,
miRNA-182, miRNA-4772, miRNA-574-5p,miRNA-133a were found to be upregulated 6,9-13.  Notablly, some of the miRNAs
(miRNA -150, miRNA-223, miRN -146a and miRNA-16) were found to be upregulated
in a particular specific stage of the sepsis but same miRNAs were found to be differntially
expressed in the different component of blood 5, 9, 11, 14. Recent studies have shown seven miRNAs, miRNA-132, miRNA-146a,
miRNA-155, miRNA-223, miRNA-15b, miRNA-126 and miRNA-7i were found to induce
inflammation and infection during sepsis in humans 5. These miRNA regulate the inflammatory response though the
activation of toll like receptor (TLR) signaling in macrophages and monocytes. TLRs
present over human immune cells in the blood circultion can recognise the lipopolysaccharide
and endotoxin to initiate the downstream NF-KB signaling.
The NF-?B transcription  factor contains
the proteins p50 and p65, which form heterodimers and are transferred to the
nucleus to activate the expression of inflammatory genes. The TLR-4 and the
several proteins are negatively regulated by the above mentioned miRNAs 15.
These miRNAs mediated  post
transcriptional suppression of several genes leads to the critical host-cell
regulatory immune responses to microbial infection.Therefore these miRNAs can
be used as a potential molecular markers in  diagnosis of sepsis infection as they were
found in the blood circulation.  1.            Gabay, C. and I. Kushner, Acute-phase proteins and other systemic
responses to inflammation. N Engl J Med, 1999. 340(6): p. 448-54.2.            Théry,
C., M. Ostrowski, and E. Segura, Membrane
vesicles as conveyors of immune responses. Nature reviews immunology, 2009.
9(8): p. 81-593.3.            Okamura,
K., et al., The regulatory activity of
microRNA* species has substantial influence on microRNA and 3? UTR evolution.
Nature structural & molecular biology, 2008. 15(4): p. 354-363.4.            Zernecke,
A., et al., Delivery of microRNA-126 by
apoptotic bodies induces CXCL12-dependent vascular protection. Sci.
Signal., 2009. 2(100): p. ra81-ra81.5.            Wang,
J.-f., et al., Serum miR-146a and miR-223
as potential new biomarkers for sepsis. Biochemical and biophysical research
communications, 2010. 394(1): p.
184-188.6.            Ma,
Y., et al., Genome-wide sequencing of
cellular microRNAs identifies a combinatorial expression signature diagnostic
of sepsis. PLoS One, 2013. 8(10):
p. e75918.7.            Sun,
X., et al., MicroRNA-181b regulates
NF-?B–mediated vascular inflammation. The Journal of clinical
investigation, 2012. 122(6): p.
1973.8.            Li,
Y., et al., Plasticity of leukocytic
exudates in resolving acute inflammation is regulated by MicroRNA and
proresolving mediators. Immunity, 2013. 39(5): p. 885-898.9.            Roderburg,
C., et al., Circulating microRNA-150
serum levels predict survival in patients with critical illness and sepsis.
PloS one, 2013. 8(1): p. e54612.10.         Wang,
L., et al., Differential expression of
plasma miR-146a in sepsis patients compared with non-sepsis-SIRS patients.
Experimental and therapeutic medicine, 2013. 5(4): p. 1101-1104.11.         Wang,
H., et al., Serum microRNA signatures
identified by Solexa sequencing predict sepsis patients’ mortality: a
prospective observational study. PLoS One, 2012. 7(6): p. e38885.12.         Wang,
H., et al., Serum miR-574-5p: a
prognostic predictor of sepsis patients. Shock, 2012. 37(3): p. 263-267.13.         Tacke,
F., et al., Levels of circulating
miR-133a are elevated in sepsis and predict mortality in critically ill
patients. Critical care medicine, 2014. 42(5): p. 1096-1104.14.         Vasilescu,
C., et al., MicroRNA fingerprints
identify miR-150 as a plasma prognostic marker in patients with sepsis.
PloS one, 2009. 4(10): p. e7405.15.         Kawagoe,
T., et al., Sequential control of
Toll-like receptor–dependent responses by IRAK1 and IRAK2. Nature
immunology, 2008. 9(6): p. 684-691.

 

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