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Cited by 230Antimicrobial Peptides and ActivitiesDermatology and Skin DiseasesAcne and Rosacea Treatments and Effects

Sebum Free Fatty Acids Enhance the Innate Immune Defense of Human Sebocytes by Upregulating β-Defensin-2 Expression

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Nakatsuji, Teruaki, Kao, Mandy C., Zhang, Liangfang, Zouboulis, Christos C., Gallo, Richard L., Huang, Chun-Ming·2010·Journal of Investigative Dermatology
DOI 10.1038/jid.2009.384PMC PMC3057125
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Abstract

Various sebum free fatty acids (FFAs) have shown antibacterial activity against a broad range of gram-positive bacteria, resulting in the suggestion that they are accountable, at least partially, for the direct antimicrobial activity of the skin surface. In this study, we examined the effects of sebum FFAs on the antimicrobial peptide (AMP)-mediated innate immune defense of human sebocytes. Incubation of lauric acid, palmitic acid, or oleic acid (OA) with human sebocytes dramatically enhanced their expression of human beta-defensin (hBD)-2, one of the predominant AMPs found in the skin, whereas remarkable increases in hBD-1, hBD-3, and human cathelicidin LL-37 were not observed. Secreted hBD-2 was detectable by western blotting in the supernatant of sebocyte culture incubated with each FFA, but not with a vehicle control. The supernatant of FFA-incubated sebocyte culture showed antimicrobial activity against Propionibacterium acnes, whereas the enhanced antimicrobial activity of human sebocytes was neutralized by anti-hBD-2 IgG. In addition, the FFA-induced hBD-2 expression was suppressed by blocking the cluster of differentiation (CD)36 fatty acid translocase on the surface of sebocytes with anti-human CD36 IgG or blocking the NF-kappaB signaling pathway with BMS-345541, a highly selective inhibitor of inhibitory kappaB kinase. These data suggest that sebum FFAs upregulate the expression of hBD-2 in human sebocytes, which may enhance the disinfecting activity of the human sebaceous gland. The FFA-induced upregulation of hBD-2 is facilitated by CD36-mediated FFA uptake and NF-kappaB-mediated transactivation. The upregulation of mouse beta-defensin 4, a mouse ortholog for hBD-2, was also observed in the hair follicle sebaceous glands of mouse ear skin after an epicutaneous application of OA, the most hBD-2-inducible FFA tested. This report highlights the potential of using FFAs as a multifunctional antimicrobial therapy agent for acne vulgaris treatment; FFAs may provide direct antibacterial activities against P. acnes and enhance the skin's innate antibacterial defense by inducing the expression of hBD-2 in sebocytes as well.

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  • Oleic acid (18:1Δ9), a major ω9 monounsaturated fatty acid of sebum triglycerides, exerts the strongest antibacterial and anti-inflammatory properties among sebaceous fatty acids and strongly enhances the innate antibacterial defence of the skin.

    “Similarly to sapienic acid, oleic acid (18:1Δ9), a major ω9 monounsaturated fatty acid of sebum triglycerides, exerts the strongest antibacterial and anti-inflammatory properties among sebaceous fatty acids and strongly enhances the innate antibacterial defence of the skin.18,19”

    From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [18]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Palmitic acid provides direct antibacterial activities against Propionibacterium acnes and enhances the skin innate antibacterial defence by inducing the expression of human β-defensin-2 (hBD2) in human sebocytes and mouse skin.

    “however, it provides direct antibacterial activities against Propionibacterium acnes (P. acnes) and enhances the skin innate antibacterial defence by inducing the expression of human β-defensin-2 (hBD2) in human sebocytes and mouse skin.18”

    From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [18]

    The Discussion reports that palmitic acid increased hBD-2 expression in human sebocytes, supporting the indirect-defense part of the claim. But it says palmitic acid did not have potent bactericidal activity against P. acnes. The mouse-skin Results tested oleic acid, not palmitic acid, and measured mouse β-defensin-4 rather than human hBD-2; page numbers are unavailable in our copy. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • Linoleic, palmitic and oleic acid, typically found in human sebum, enhanced the hBD-2 expression and antimicrobial activity of human sebocytes against P. acnes.

    “As previously described, Nakatsuji et al. found that linoleic, palmitic and oleic acid, typically found in human sebum enhanced the hBD-2 expression and antimicrobial activity of human sebocytes against P. acnes.18”

    From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [18]

    The Introduction identifies the tested acids as lauric acid (LA), palmitic acid, and oleic acid—not linoleic acid. The Discussion reports that these acids increased hBD-2 expression in human sebocytes and that their culture supernatants had antimicrobial activity against P. acnes. Page numbers were not provided in our copy. (LLM, conf=0.93)

    Experimental — accuracy not yet measured

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Authors
Nakatsuji, T., Kao, M. C., Zhang, L., Zouboulis, C. C., Gallo, R. L., & Huang, C.-M.
Affiliations
  • University of California San Diego (US)
  • Städtisches Klinikum Dessau (DE)
Corresponding author
Huang, Chun-Ming
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2010-04
Volume
130
Issue
4
Pages
985-994
ISSN
0022-202X (ISSN-L)
DOI
10.1038/jid.2009.384
PMC
PMC3057125
OpenAlex
W2113679439
Cited by
230
References
3
Citations by year
2026: 6 · 2025: 22 · 2024: 20 · 2023: 31 · 2022: 15 · 2021: 16 · 2020: 5 · 2019: 13 · 2018: 14 · 2017: 11 · 2016: 12 · 2015: 9 · 2014: 13 · 2013: 18 · 2012: 7
FWCI
8.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (1R41AR056169, R01-AI067395-01, R21-I58002-01, R21-R022754-01)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
Keywords
human beta-defensin 2, sebocytes, innate immunity, antimicrobial peptides, Propionibacterium acnes, NF-κB signaling, oleic acid, lauric acid, palmitic acid, cathelicidin LL-37, acne, sebaceous glands
MeSH terms
Acne Vulgaris, Animals, Cell Line, Transformed, Fatty Acids, Nonesterified, Female, Humans, Immunoglobulin G, Lauric Acids, Mice, Inbred ICR, Propionibacterium acnes, Sebaceous Glands, Sebum, Signal Transduction, Up-Regulation, NF-kappa B, Gram-Positive Bacterial Infections, Hair Follicle, CD36 Antigens, Oleic Acid, Palmitic Acid, beta-Defensins, Mice

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