Serine deficiency exacerbates psoriatic skin inflammation

[Fred]

This study investigated the association between serine metabolism and psoriatic skin inflammation.

Quote:

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Background:
Serine metabolism is crucial for tumor oncogenesis and immune responses. S-adenosyl methionine (SAM), a methyl donor, is typically derived from serine-driven one-carbon metabolism. However, the involvement of serine metabolism in psoriatic skin inflammation remains unclear.

Objectives:
To investigate the association between serine metabolism and psoriatic skin inflammation.

Methods:
Clinical samples were collected from patients with psoriasis and the expression of serine biosynthesis enzymes was evaluated. The HaCaT human keratinocyte cell line was transfected with small interfering RNA (siRNA) of key enzyme or treated with inhibitors. RNA sequencing and DNA methylation assays were performed to elucidate the mechanisms underlying serine metabolism-regulated psoriatic keratinocyte inflammation An imiquimod (IMQ)-induced psoriasis mouse model was established to determine the effect of the SAM administration on psoriatic skin inflammation.

Results:
The expression of serine synthesis pathway enzymes, including the first rate-limiting enzyme in serine biosynthesis, phosphoglycerate dehydrogenase (PHGDH), was downregulated in the epidermal lesions of patients with psoriasis compared with that in healthy controls. Suppressing PHGDH in keratinocytes promoted the production of proinflammatory cytokines and enrichment of psoriatic-related signaling pathways, including the tumor necrosis factor-alpha (TNF-α) signaling pathway, interleukin (IL)-17 signaling pathway, and NF-κB signaling pathway. In particular, PHGDH inhibition markedly promoted the secretion of IL-6 in keratinocytes with or without IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α (mix) stimulation. Mechanistically, PHGDH inhibition upregulated the expression of IL-6 by inhibiting SAM-dependent DNA methylation at the promoter and increasing the binding of myocyte enhancer factor 2A. Furthermore, PHGDH inhibition increased the secretion of IL-6 by increasing the activation of NF-κB via SAM inhibition. SAM treatment effectively alleviated IMQ-induced psoriasis-like skin inflammation in mice.

Conclusions:
Our study revealed the crucial role of PHGDH in antagonizing psoriatic skin inflammation and indicated that targeting serine metabolism may represent a novel therapeutic strategy for treating psoriasis.

Source: onlinelibrary.wiley.com

*Early view funding unknown 

[Caroline]

Again not aiming for the real cause, but trying to intercept or suppress the active disease.

[Fred]

Again not aiming for the real cause, but trying to intercept or suppress the active disease.

Three months late for an answer from one of our members ................................ not bad.

[Caroline]

Again not aiming for the real cause, but trying to intercept or suppress the active disease.

Three months late for an answer from one of our members ................................ not bad. 

I knew it was still lying here…. But those reports are always very difficult to read. So I stalled…

[Fred]

Again not aiming for the real cause, but trying to intercept or suppress the active disease.

Three months late for an answer from one of our members ................................ not bad. 

I knew it was still lying here…. But those reports are always very difficult to read. So I stalled…

Sorry I worded it wrong, it wasn't meant as a knock to you Caroline, more of an observation of the general lack of members posting in the public boards these days.

[Caroline]

Again not aiming for the real cause, but trying to intercept or suppress the active disease.

Three months late for an answer from one of our members ................................ not bad. 

I knew it was still lying here…. But those reports are always very difficult to read. So I stalled…

Sorry I worded it wrong, it wasn't meant as a knock to you Caroline, more of an observation of the general lack of members posting in the public boards these days. 

O… I didn’t experience it as that.
I normally read all threads, also these research threads. And I was very late with this one.
I still am surprised that there is hardly any research visible that is aiming at the discovery of the real cause with the purpose of then treating the cause instead of the manifestation of the disease.
As there are quite some people, like Alan, who fight there disease with there food and have result, I have the idea that they are really treating the cause of there disease, they take away what triggers it or they change something in the energy system of the body, that then seems to repair itself.

[Turnedlight]

Does anybody know what serine is?

[Kat]

I glance at these, but usually have nothing to add as most of it goes over my head to be honest.

[Caroline]

Does anybody know what serine is?

I had to look it up too. It is an amino-acid.... which does not say me anything more.
BUT.. trying to read the information it seems that it is in the pathway of different reactions in the body that finally cause psoriasis on the skin. Therefore if you break that path = that reaction, other reactions will also not be possible and that influences the psoriasis.

@kat I also am not able to understand those chemical stuff, but I try to find the connection in what they are writing, sometimes looking up things and that gives a little insight in what is happening.

[Fred]

Thank you Caroline.

@Kat I don't have a clue either to be honest, I try to understand them and sometimes get it. But I just post the news and hope someone will know enough to explain in easy terms.