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Skin Cutibacterium acnes Mediates Fermentation to Suppress the Calcium Phosphate-Induced Itching: A Butyric Acid Derivative with Potential for Uremic Pruritus
- Source :
- Journal of Clinical Medicine, Vol 9, Iss 2, p 312 (2020), Journal of Clinical Medicine, Volume 9, Issue 2
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Pruritus and inflammation associated with accumulation of calcium phosphate (CaP) under the skin are common problems among dialysis patients with chronic kidney disease (CKD). The role of skin commensal microbiota in the CaP-induced uremic pruritus remains uncharacterized. Skin Cutibacterium acnes (C. acnes) can solubilize CaP by the production of short-chain fatty acids (SCFAs), such as butyric acid, through glucose fermentation. Like butyric acid, the N-[2-(2-Butyrylamino-ethoxy)-ethyl]-butyramide (BA-NH-NH-BA), a butyric acid derivative, remarkably induced acetylation of histone H3 lysine 9 (AcH3K9) in keratinocytes. Topical application of fermenting C. acnes, butyric acid or BA-NH-NH-BA onto mouse skin effectively ameliorated CaP-induced skin itching, interleukin (IL)-6 up-regulation in keratinocytes, and extracellular signal-regulated kinase (ERK) 1/2 activation in dorsal root ganglia (DRG). Activation of ERK 1/2 by CaP was markedly reduced in IL-6 knockout mice. Genus Cutibacterium was detected in relatively low abundance in itchy skin of patients with CKD. Our results identify a role for the skin fermenting C. acnes in ameliorating CaP-induced activation of IL-6/p-ERK signaling and resulting skin inflammation. Furthermore, we provide evidence for the potential therapeutic efficacy of BA-NH-NH-BA as a postbiotic for the treatment of uremic pruritus.
- Subjects :
- Uremic pruritus
030232 urology & nephrology
chemistry.chemical_element
lcsh:Medicine
Inflammation
Calcium
Pharmacology
cap
Article
Butyric acid
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Extracellular
fermentation
030304 developmental biology
0303 health sciences
integumentary system
Kinase
business.industry
lcsh:R
Interleukin
General Medicine
ba-nh-nh-ba
medicine.disease
C. acnes
chemistry
ckd
c. acnes
Itching
medicine.symptom
business
Subjects
Details
- Language :
- English
- ISSN :
- 20770383
- Volume :
- 9
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Medicine
- Accession number :
- edsair.doi.dedup.....de6842d34a80eacc6490fd4ecad5b1e2