Histamine Suppresses Epidermal Keratinocyte Differentiation And Impairs Skin Barrier Function In A H

paymanz

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Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model


Abstract
Background

Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are abundant in inflamed skin and thus may contribute to disease pathogenesis.
Methods

Human primary keratinocytes were cultured under differentiation-promoting conditions in the presence and absence of histamine, histamine receptor agonists and antagonists. The expression of differentiation-associated genes and epidermal junction proteins was quantified by real-time PCR, Western blot, and immunofluorescence labeling. The barrier function of human skin models was tested by the application of biotin as tracer molecule.
Results

The addition of histamine to human keratinocyte cultures and organotypic skin models reduced the expression of the differentiation-associated proteins keratin 1/10, filaggrin, and loricrin by 80–95%. Moreover, the addition of histamine to skin models resulted in the loss of the granular layer and thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R agonist, 2-pyridylethylamine, suppressed keratinocyte differentiation to the same extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R, virtually abrogated the effect of histamine. The expression of tight junction proteins zona occludens-1, occludin, claudin-1, and claudin-4, as well as that of desmosomal junction proteins corneodesmosin and desmoglein-1, was down-regulated by histamine. The tracer molecule biotin readily penetrated the tight junction barrier of skin cultures grown in the presence of histamine, while their diffusion was completely blocked in nontreated controls.
Conclusions

Our findings suggest a new mechanism by which mast cell activation and histamine release contribute to skin barrier defects in inflammatory skin diseases.
 

cats

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Interesting. I've been having some gut issues over the past couple years (I suspect H. pylori) and I know that this can cause a lot of histamine activity. During this time, I've noticed some skin thinning and loss of elasticity. It's especially noticeable on the pads of my feet, with my feet being much more prone to soreness while standing or walking. I wonder if suppressing histamine would allow for regrowth?
 

Terma

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Thanks for the article and bump.
Interesting. I've been having some gut issues over the past couple years (I suspect H. pylori) and I know that this can cause a lot of histamine activity. During this time, I've noticed some skin thinning and loss of elasticity. It's especially noticeable on the pads of my feet, with my feet being much more prone to soreness while standing or walking. I wonder if suppressing histamine would allow for regrowth?

I don't know but I have most those problems distinctly, and I know for myself that cortisol has been a major point of deterioration on a chronic basis: JCI - 11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects
All of the above maybe?
 
OP
P

paymanz

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Histamine H1 and H2 Receptor Antagonists Accelerate Skin Barrier Repair and Prevent Epidermal Hyperplasia Induced by Barrier Disruption in a Dry Environment - ScienceDirect

Keratinocytes have histamine H1 and H2 receptors, but their functions are poorly understood. To clarify the role of histamine receptors in the epidermis, we examined the effects of histamine receptor antagonists and agonists applied epicutaneously on the recovery of skin barrier function disrupted by tape stripping in hairless mice. Histamine H2 receptor antagonists famotidine and cimetidine accelerated the recovery of skin barrier function, but histamine and histamine H2 receptor agonist dimaprit delayed the barrier repair. Application of compound 48/80, a histamine releaser, also delayed the recovery. Imidazole, an analog of histamine, had no effect. The histamine H1 receptor antagonists diphenhydramine and tripelennamine accelerated the recovery. Histamine H3 receptor agonist Nα-methylhistamine and antagonist thioperamide had no effect. In addition, topical application of famotidine or diphenhydramine prevented epidermal hyperplasia in mice with skin barrier disrupted by acetone treatment in a dry environment (humidity <10%) for 4 d. In conclusion, both the histamine H1 and H2 receptors in the epidermis are involved in skin barrier function and the cutaneous condition of epidermal hyperplasia
 

LeeLemonoil

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Sep 24, 2016
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Thanks for the article and bump.


I don't know but I have most those problems distinctly, and I know for myself that cortisol has been a major point of deterioration on a chronic basis: JCI - 11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects
All of the above maybe?

@Terma, see also:

https://raypeatforum.com/community/...icoid-induced-skin-atrophy.19310/#post-261352

Ketotifen Prevents Skin Aging/wrinkles Due To UV Light
 

LeeLemonoil

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Sep 24, 2016
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So these studies on skin-regeneration once more confirm the "duality" between glucocorticoids and functioning thyroid hormone levels in tissues.
If you run on cortisol you'll end up with degenerated, defunct tissues, while T3 can restore it and would prevent untimely degeneration in the first place.

Intersting that blocking 11beta-HSD will also lead to regeneration and not only prevention of tissue-breakdown. Emodin is a potent 11b-HSD1 ihibitor, and probably Theanine and Green Tea/White Tr extracts.

With topical TRIA or T3 and Emodin one would probably achieve substantia topical "anti-age" skin effects. In addition to staples like E,A, B3 etc...
 

GorillaHead

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So how can we achieve this anti histmaine effects without using pharma antagonist. I am specifically looking for an h1 antagonist or finding way to significantly reducing substrates to bind.

vitamin C.
Copper.

what else?
 
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