Tier 4 — mechanistic

Nicotinamide mononucleotide and nicotinamide riboside attenuate cytokine production in human keratinocytes via suppression of p38 Pathway

Chen Xie, Maria Alejandra Molina Velandia, Samantha Marecek, Miriam Khalil, Jijun Hao
Molecular Biology Reports 2026 53(1):459

Bibliography

PubMed
PMID 41779073
PubMed Central
PMC12960338
DOI
10.1007/s11033-026-11615-2
Funding
Open access funding provided by SCELC (Statewide California Electronic Library Consortium). The study was supported by an intramural fund from Western University of Health Sciences to J.H.
Competing interests
The authors declared no competing interests and no relevant financial or non-financial interests.

Study snapshot

DesignIn vitro mechanistic brief report using cytokine-stimulated human keratinocytes, RT-qPCR, cell-viability assays and Western blot signaling analysis.
ModelHuman HaCaT keratinocytes stimulated with TNF-α and IFN-γ as an in-vitro model of atopic-dermatitis-associated epidermal inflammation.
SampleThree independent biological experiments per condition (n=3); no human participants were enrolled.
InterventionNMN pretreatment at 0.5, 1 and 5 mM or NR at 0.5, 1 and 2 mM for 1 hour before TNF-α/IFN-γ stimulation.
Duration1-hour precursor pretreatment followed by cytokine stimulation; gene-expression endpoints at 24 hours, with signaling assays at acute time points.
EndpointsIL-1β mRNA; MDC/CCL22; CCL5/RANTES; CCL17/TARC; IL8; TSLP; p38 MAPK phosphorylation; AKT phosphorylation; ERK phosphorylation; NF-κB phosphorylation; JNK phosphorylation; Cell viability

What the study showed, in plain terms

Researchers used cultured human keratinocytes exposed to TNF-α and IFN-γ to mimic an inflammatory skin environment and then tested whether NMN or nicotinamide riboside altered the response.

NMN dose-dependently reduced several inflammatory cytokine and chemokine transcripts, including IL-1β, CCL22, CCL5, CCL17, IL8 and TSLP. Both NMN and NR suppressed p38 MAPK phosphorylation without reducing cell viability under the experimental conditions.

This is current mechanistic evidence from human skin cells—not a clinical trial. It does not show that swallowing NMN treats atopic dermatitis, improves wrinkles or produces visible anti-aging effects in people.

Key findings

  • NMN significantly and dose-dependently reduced IL-1β, CCL22/MDC, CCL5, CCL17/TARC, IL8 and TSLP expression in cytokine-stimulated HaCaT keratinocytes.
  • NR reduced most of the same inflammatory mediators but did not significantly reduce IL-1β under the study conditions.
  • Both NMN and NR suppressed p38 MAPK phosphorylation.
  • AKT, ERK, NF-κB and JNK phosphorylation were not significantly altered under the reported conditions.
  • Neither NMN nor NR reduced keratinocyte viability at the tested concentrations.

What this study can and cannot tell us

The work is entirely in vitro. HaCaT cells are an immortalized keratinocyte line and do not reproduce the full immune, barrier, vascular and microbiome environment of living human skin.

The millimolar concentrations applied directly to cells cannot be assumed to occur in skin after ordinary oral NMN supplementation.

The model measures inflammatory signaling rather than patient outcomes such as eczema severity, itch, barrier function, wrinkles, elasticity or pigmentation.

The paper supports a mechanistic hypothesis for skin inflammation, not treatment of atopic dermatitis or clinical skin rejuvenation.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology