ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in...

[Kati]

News from NCNED/Griffith University

NCNED is pleased to announce the release of our latest publication entitled “ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.”

This paper identifies pathological changes in vital signalling pathways in ME/CFS. These pathways exert a major influence over cell functioning suggesting important fundamental steps in the development of the pathomechanism of ME/CFS. The full article can be accessed by following the link below.

http://translational-medicine.biomedcentral.com/…/s12967-01…

We sincerely thank all of our supporters including the Stafford Fox Foundation, Alison Hunter Memorial Foundation, the Mason Foundation, the Queensland Government and all particpants who have contributed to this important research outcome.

There are more publications to come.

ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patient
Teilah Kathryn Huth, Donald Staines and Sonya Marshall-Gradisnik
Journal of Translational Medicine201614:97
DOI: 10.1186/s12967-016-0859-z
Huth et al. 2016

Received: 16 September 2015

Accepted: 10 April 2016

Published: 21 April 2016



Abstract
Background
Natural Killer (NK) cell effector functions are dependent on phosphorylation of the mitogen-activated protein kinases (MAPK) pathway to produce an effective immune response for the clearance of target cells infected with viruses, bacteria or malignantly transformed cells. Intracellular signals activating NK cell cytokine production and cytotoxic activity are propagated through protein phosphorylation of MAPKs including MEK1/2, ERK1/2, p38 and JNK. Reduced NK cell cytotoxic activity is consistently reported in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients and intracellular signalling by MAPK in NK cells remains to be investigated. Therefore, the purpose of this paper was to investigate MAPK downstream signalling molecules in NK cell phenotypes from CFS/ME patients.

Methods
Flow cytometric protocols were used to measure phosphorylation of the MAPK pathway in CD56brightCD16dim/− and CD56dimCD16+ NK cells following stimulation with K562 tumour cells or phorbol-12-myristate-13-acetate plus ionomycin. NK cell cytotoxic activity, degranulation, lytic proteins and cytokine production were also measured as markers for CD56brightCD16dim/− and CD56dimCD16+NK cell function using flow cytometric protocols.

Results
CFS/ME patients (n = 14) had a significant decrease in ERK1/2 in CD56dimCD16+ NK cells compared to the non-fatigued controls (n = 11) after incubation with K562 cells. CD56brightCD16dim/− NK cells from CFS/ME patients had a significant increase in MEK1/2 and p38 following incubation with K562 cells.

Conclusions
This is the first study to report significant differences in MAPK intracellular signalling molecules in CD56dimCD16+ and CD56brightCD16dim/− NK cells from CFS/ME patients. The current results highlight the importance of intracellular signalling through the MAPK pathway for synergistic effector function of CD56dimCD16+ and CD56brightCD16dim/− NK cells to ensure efficient clearance of target cells. In CFS/ME patients, dysfunctional MAPK signalling may contribute to reduced NK cell cytotoxic activity.

 

[lansbergen]

@Jonathan Edwards

Anything known about epidermal growth factor and Rituximab?

 

[Snow Leopard]

Non facebook link:
http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0859-z

I will have a look at this sometime as I spent a bit of time last year looking at these kinases and growth factors...

The finding however is specific to the CD56dimCD16+ NK cells in question, so it doesn't in itself explain anything about ME or CFS.

 

[deleder2k]

New findings regarding the pathology of Chronic Fatigue Syndrome (CFS) are bringing Griffith University researchers closer to identifying the cause of this disabling illness.

This is the news from a team at the National Centre for Neuroimmunology and Emerging Diseases at the Menzies Health Institute Queensland.

Professors Marshall-Gradisnik and Don Staines and their research team have identified significant impairments in cellular function of people with CFS.

CFS -- sometimes known as ME (myalgic encephalomyelitis) -- is a complex illness characterized by impaired memory and concentration, metabolic, cardiac, gut and immune dysfunction and debilitating muscle pain and fatigue on exertion (also known as neuroimmune exhaustion).

It is estimated that the prevalence rate of CFS/ME worldwide is between 1 and 2 per cent.

"While the patho-mechanism of CFS/ME is unknown, these recent findings by NCNED researchers provide further evidence for the pathology of this illness," says Professor Sonya Marshall-Gradisnik, who speaks as we approach International CFS Awareness Day on Thursday May 12.

Published in the Journal of Translational Medicine, the results report significant differences in intracellular signalling of cells with CFS patients.

"In this group, we see that dysfunctional signalling may contribute to impaired cell activity. These findings are consistent with our previous findings and align with the presentation of symptoms in patients," says Professor Staines.

The current research findings build upon recent discoveries including novel identification of key genetic changes in cells of the immune system.

The NCNED -- internationally recognised for research into CFS/ME -- will present a seminar on current research findings on this disease on International CFS/ME Awareness Day, Thursday May 12 at Griffith University, Gold Coast Campus, commencing 1pm, location G17, Lecture theatre 3.

Griffith University will also be illuminating the Griffith Health Centre in blue to further help raise awareness for CFS/ME.

https://www.sciencedaily.com/releases/2016/05/160510093906.htm