alexa Receptors for Interleukins and Tumor Necrosis Factor are Important in Assessing their Roles in CNS Disorders | Open Access Journals
ISSN: 2155-9899
Journal of Clinical & Cellular Immunology
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Receptors for Interleukins and Tumor Necrosis Factor are Important in Assessing their Roles in CNS Disorders

Patricia Szot1,2*

1Northwest Network for Mental Illness Research, Education, and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle, Washington, USA

2Department of Psychiatry and Behavioral Science, University of Washington, Seattle, Washington, USA

*Corresponding Author:
Patricia Szot
Northwest Network for Mental Illness Research
Education, and Clinical Center
Veterans Administration Puget Sound Health Care System, Seattle, Washington, USA
Tel: 206-277-5052
E-mail: [email protected]

Received date: July 11, 2017; Accepted date: August 24, 2017; Published date: August  30, 2017

Citation: Szot P (2016) Receptors for Interleukins and Tumor Necrosis Factor are Important in Assessing their Roles in CNS Disorders. J Clin Cell Immunol 8:519. doi: 10.4172/2155-9899.1000520

Copyright: © 2017 Szot P. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Clinical & Cellular Immunology

Abstract

The immune-to-brain communication is still in its infancy but there is a great deal of data to suggest its importance in several central nervous system (CNS) disorders. There are three cytokines, interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha (TNFα), which have emerged to have a major role in the CNS and in different CNS disorders. The majority of the published work to date has been on examining changes in the levels of these proteins in the CNS with inflammation; but recent work from our laboratory has shown the receptors for these cytokines may also be an important factor in neuroinflammation mediated CNS disorders, because these receptors are solely localized to neurons and are modified when their ligands levels are elevated. For neuroinflammation and the increase in cytokine levels (either by glia or neurons) to influence neurons and consequently affect the development of CNS disorders, the location of these cytokines receptors on neuronal populations may be the key.

Keywords

Alzheimer's disease; CNS disorders; Neuroinflammation

Introduction

Over recent year’s inflammation, specifically neuroinflammation, has received a great deal of attention especially in reference to central nervous system (CNS) disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, and traumatic brain injury (TBI) [1-5]. It has become apparent that an immune response can regulate the CNS. This connection has been termed the immune-to-brain communication [6-9]. Understanding this connection between the immune system and CNS function is in its infancy. However, it is clear that an immune response by the peripheral administration of the inflammatory agent, lipopolysaccharide (LPS), can result in excitation in specific brain regions by detecting an increase in the expression of the neuronal immediate early gene Fos [10-16]. The immune response with the involvement of a neuroinflammatory response is complex and involves multiple proteins with a complex time course. Research has shown cytokines play an important role in mediating the effects of LPS, with specific interest in interleukin (IL)-1, IL-6 and tumor necrosis factor alpha (TNFα). Stimulation of Fos can be mediated by IL-1β (a subtype of IL-1) [17-19] and IL-6 [15,19] supporting the immune-to-brain communication. At the present time, the link between the immune system to CNS disorders appears to be strongest with depression and AD.

The behavior observed following LPS induced “sickness” (cytokineinduced sickness behavior) is similar to depression, such as withdrawal from physical and social environment, pain, malaise, and anhedonia [20-23]. The cytokines involved in mediating these behaviors are mainly IL-1β and TNFα, with IL-6 having some role [20,24,25]. In addition, administration of LPS or these cytokines ultimately results in depressive-like behavior in two common animals’ models of depression: the forced swim test and the tail suspension test [20].Cytokines are proposed to mediate depression because administration of LPS, IL-1 or IL-6 can enhance the hypothalamic-pituitary-adrenal (HPA) axis, a major component in the development of depression; and LPS, IL-1 or IL-6 alters levels of norepinephrine (NE) and serotonin (5HT), two neurotransmitters systems mediating depression [21,26,27].

Neuroinflammation’s role in the progression of AD has been growing with the identification of TREM2 and CD33 varients, two markers indicating the presence of neuroinflammation, as major risk factors in the development of AD [28-32]. The role of neuroinflammation in AD is also apparent from epidemiological, retrospective studies that demonstrated nonsteroidal antiinflammatory drugs to reduce the incidence of AD [33-36]. Some studies have detected elevated IL-1, IL-6 and TNFα protein in postmortem AD tissue in neuronal and non-neuronal cells [35,37], although there is no change in mRNA levels [38,39]. There is a relationship between inflammation and the generation of cytokines and the presence of β-amyloid (Aβ), a classic neuropathological marker of AD [40,41]. Elevated levels of IL-1, IL-6 and TNFα the activity of neurons (long-term potentiation), specifically in the hippocampus, thereby impairing cognition/memory [42-48].direct effect on CNS neurons. Following administration of multiple LPS injections, there was a significant increase in IL-6 mRNA in the spleen and in the brain of 5 of the 9 animals. The increase in IL-6 mRNA in the brain due to LPS administration was observed only in non-neuronal cells throughout the brain, the neuronal expression remained unchanged. Interestingly, the receptor for IL-6, IL-6R mRNA was not observed in the non-neuronal population that expressed IL-6 mRNA following LPS. IL-6R mRNA was significantly elevated in all the brain regions that exhibited neuronal expression, except for the cerebellum ONLY in the animals that exhibited non-neuronal IL-6 mRNA in response to LPS, indicating that a non-neuronal response to LPS can directly (or indirectly) affect neurons which express the receptor for IL-6 [49]. In the hippocampus however, IL-6R mRNA was elevated in all the animals that were administered LPS, even the LPS treated animals that did not exhibit IL-6 non-neuronal expression, suggesting the hippocampus to be sensitive to LPS. This data supports the relationship between inflammation due to LPS and depression that was discussed above. Also, the Szot et al., study indicates that the peripheral response of IL-6R mRNA following multiple LPS injections was different from the central response; in the spleen IL-6R mRNA was reduced in response to elevated IL-6 mRNA, but in the brain IL-6R mRNA was elevated in most but not all brain regions in response to elevated IL-6 mRNA expressed [49].

Similarly, a change in TNFɑ, no matter if TNFα is generated in non-neuronal or neuronal cells in the brain, will directly affect neuronal cells because TNFα receptor 1 mRNA is solely localized to neurons [6]. The same applies for IL-1, there are two variants of IL-1 (α and β), but both of these variants of IL-1 bind to the IL-1 receptor (IL-1R), which is expressed in neurons, particularly in the hippocampus [50,51]. Little is known about alterations in these receptors under different conditions including inflammation.

As our knowledge concerning the role of neuroinflammation in different CNS disorders is increasing, and that specific cytokines like IL-1, IL-6 and TNFα are extremely important in mediating these changes in behavior or neuronal activity; however, it is apparent that their receptors are also extremely important in mediating their effects and producing the neuronal alterations that are associated with these CND disorders.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 169
  • [From(publication date):
    August-2017 - Oct 23, 2017]
  • Breakdown by view type
  • HTML page views : 139
  • PDF downloads :30
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords