MicroRNAs in the Cholinergic Anti-Inflammatory Pathway: Immunotherapy


Immunotherapy: Open Access was congratulating its authors of most cited articles. The article entitled “MicroRNAs in the Cholinergic Anti-Inflammatory Pathway: ProspectiveTherapeutic Targets for Inflammatory Diseases” which was written by Yang Sun and Xia Liu was mostly cited article which was published in 2016 from Department of Pharmacology, Second Military Medical University School of Pharmacy, Shanghai, China by Yang Sun and Xia Liu.


It is the editorial published by the editor Xia Liu who was one of the eminent editorial board members of Immunotherapy: Open Access.


The article will be as follows: The host inflammatory response can be self-limited or progress toimmunological and inflammatory diseases. It has been well known thathumoral anti-inflammatory  mechanisms,  including  IL-10,  TGF-β1,glucocorticoids  and  other  cytokine  inhibitors,  can  protect  tissueagainst cytokine-induced damage in humans. Recent advances haveidentified a brain to immune system mechanisms, termed cholinergicanti-inflammatory pathway (CAP). Briefly, the vagus nerve senses andconveys the inflammatory signal to the brain, and the brain, via vagalsecretion of acetylcholine (ACh) which binds a7 nicotinic receptors onmacrophages (α7nAchR), suppresses peripheral cytokine productionand guard against tissue damage. The brain maintains immunehomeostasis  via  in  real  time  monitoring  and  adjusting  theinflammatory response, and this regulation manner is quicker, effectiveand  localized  when  compared  to  humoral  ones.  Activation  of  this‘‘cholinergic reflex’’ has been found effective in various inflammatorydisease  such  as  sepsis,  rheumatoid  arthritis,  Crohn’s  disease,  andcerebral and myocardial ischaemia. However, vagus nerve stimulationin humans is an invasive procedure and is not feasible under manycircumstances. Pharmacological activation, such as nicotine, a non-specific α7nAchR agonist, is associated with severe side effects andtoxicity. Novel specific and effective targets activating CAP are stillneeded for the therapeutic interventions in inflammatory diseases.MicroRNAs  (miRNAs)  are  non-coding  transcripts  of  18-25nucleotides,  and  they  usually  target  mRNAs  to  modulate  geneexpression by 1.2 to 4.0 fold rather than acting as on-off switches forgenes. miRNAs have been found to contribute to both neuronal andimmune  cell  fate,  but  their  involvement  in  the  neuroimmuneinterface of CAP remains largely unknown. Several miRNAs assistingvagal cholinergic anti-inflammatory activity, named cholinomiRs, hasbeen identified  only  recently,  especially  miR-124  and  miR-132.They are reported to be induced by LPS challenge and their treatmentcould potentiate the CAP and attenuate inflammation.α7nAChR is essential for the cholinergic anti-inflammatory action. Downstream signal molecules that link α7nAChR activation andpro-inflammatory  cytokine  production  will  be  potential  targets  fortherapeutic  interventions  that  modulate inflammatory  responses.MiR-124 is reported to be induced after LPS and α7nAChR activation,which in turn targets signal transducer and activator of transcription 3(STAT3)  and  TNF-α  converting  enzyme  (TACE)  and  reduces  IL-6production and TNF-α release. MiR-124 knockdown abolished thenicotine’s  cholinergic anti-inflammatory  action  in  LPS-triggeredmacrophages and mice. Furthermore, miR-124 overexpression couldsignificantly increase the survival rate of mice that were given a lethaldose of  LPS. Therefore,  miR-124  might  be  a  valuable  target  intreating  sepsis.  Moreover,  miR-124  shows  therapeutic  potential  inother inflammatory-related diseases. MiR-124 mediates the protectiverole  of  nicotine  in  DSS-induced  mice  colitis,  and  miR-124reduction  promoted inflammation  and  pathogenesis  in  ulcerativecolitis patients. Abnormal expression of miR-124 is also found inrheumatoid  arthritis  (RA)  patients  and  ankylosing  spondylitis  (AS)patients.  Forced  expression  of  miR-124  repressed  adjuvant-inducedarthritis  (AIA)  in  rats  by  decreasing  synoviocyte  proliferation,leukocyte infiltration,  and  cartilage  or  bone  destruction  throughsuppressing  RANKL  and  NFATc1.  MiR-124  overexpressionsuppresses  experimental  autoimmune  encephalomyelitis  (EAE)  bydeactivating microglia, a kind of macrophages resident in the brainand spinal cord, via the C/EBP-α-PU.1 pathway . Microinjection ofmiR-124  into  the  peritoneum,  which  then  be  transported  bymacrophages  to  the  site  of  spinal  cord  injury,  could  decrease  theinfiltration of macrophages and therefore ameliorate spinal cord injury.  MiR-124  also  shows  its  therapeutic effect  in  the  treatment  ofglioma, B-cell lymphomas and even liver cancers by regulating STAT3or other targets. Therefore, miR-124 is a promising candidatetarget for a broad spectrum of inflammatory diseases.


For more info regarding this manuscript please go through the below link: https://www.longdom.org/open-access/micrornas-in-the-cholinergic-antiinflammatory-pathway-prospectivetherapeutic-targets-for-inflammatory-diseases-2471-9552-1000e106.pdf


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