Influence of substance-P on cultured sebocytes

  • Weon Ju LeeEmail author
  • Hong Dae Jung
  • Hyun Joo Lee
  • Byung Soo Kim
  • Seok-Jong Lee
  • Do Won Kim
Original Paper


Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. Culture of sebocytes provides a new insight into the participation of neuropeptides, notably substance P (SP), in the pathophysiology of acne. To examine the possible involvement of neurogenic factors in the pathogenesis of acne, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), peroxisome proliferators activated receptors-γ (PPAR-γ) on the cultured sebocytes stimulated by SP. IL-1 is primarily proinflammatory cytokines to stimulate the expression of genes associated with inflammation. IL-6 is a pleiotropic cytokine with a wide range of biological activities and regulates inflammation. TNF-α is a pleiotropic pro-inflammatory cytokine that exerts multiple biologic effects. PPAR-γ is a nuclear hormone receptor and plays a unique role in stimulating sebocyte lipogenesis. More numerous immunoreactivity to IL-1, IL-6, TNF-α and PPAR-γ and increased RNA amplification for IL-1, IL-6, TNF-α and PPAR-γ were observed after addition of SP compared with the control. This study reveals that SP is involved in the pathogenesis of acne.


Acne Sebocyte Sebocyte culture Substance-P 


  1. 1.
    Alestas T et al (2006) Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med 84:75–87PubMedCrossRefGoogle Scholar
  2. 2.
    Benfenati A, Brillanti F (1939) Sulla distribuzione delle ghiandole sebacee nella cute del corpo umino. Arch Ital Dermatol 15:33–42Google Scholar
  3. 3.
    Cunliffe WJ (1989) Acne. Martin Dunitz, LondonGoogle Scholar
  4. 4.
    Fujie T, Shikiji T, Uchida N et al (1996) Culture of cells derived from the human sebaceous glands under serum-free conditions without a biological feeder layer or specific matrices. Arch Dermatol Res 288:703–708PubMedCrossRefGoogle Scholar
  5. 5.
    Katsambas A, Papakonstantinou A (2004) Acne: systemic treatment. Clin Dermatol 22:412–418PubMedCrossRefGoogle Scholar
  6. 6.
    Marta Guarna M, Coulson R, Rubinchik E (2006) Anti-inflammatory activity of cationic peptides: application to the treatment of acne vulgaris. FEMS Microbiol Lett 257:1–6PubMedCrossRefGoogle Scholar
  7. 7.
    Nadel JA, Borson DB (1991) Modulation of neurogenic inflammation by neutral endopeptidase. Am Rev Respir Dis 143:33–36Google Scholar
  8. 8.
    Olerud JE, Usui MJ, Seckin D, Chui DS, Haycox CL, Song I-S, Ansel JC, Bunnett NW. (1999) Neutral endopeptidase expression and distribution in human skin and wounds. J Invest Dermatol 112:873–881PubMedCrossRefGoogle Scholar
  9. 9.
    Rohleder N, Wolf JM, Herpfer I, Fiebich BL, Kirschbaum C, Lieb K (2006) No response of plasma substance P, but delayed increase of interleukin–1 receptor antagonist to acute psychosocial stress. Life Sci 22;78(26):3082–3089CrossRefGoogle Scholar
  10. 10.
    Thielitz A et al (2007) Inhibitors of dipeptidyl peptidase IV and aminopeptidase N target major pathogenetic steps in acne initiation. J Invest Dermatol 127:1042–1051PubMedCrossRefGoogle Scholar
  11. 11.
    Toyoda M, Morohashi M (2001) Pathogenesis of acne. Med Elect Microsc 34:29–40CrossRefGoogle Scholar
  12. 12.
    Toyoda M, Makino T, Kagoura M, Morohashi M (2001) Expression of neuropeptide—degrading enzymes in alopecia areata: an immunohistochemical study. Br J Dermatol 144:46–54PubMedCrossRefGoogle Scholar
  13. 13.
    Toyoda M, Nakamura M, Makino T et al (2002) Sebaceous glands in acne patients express high levels of neutral endopeptidase. Exp Dermatol 11:241–247PubMedCrossRefGoogle Scholar
  14. 14.
    Toyoda M, Nakamura M, Morohashi M (2002) Neuropeptides and sebaceous glands. Eur J Dermatol 12:422–427PubMedGoogle Scholar
  15. 15.
    Trivedi NR et al (2006) Peroxisome proliferators-activated receptors increase human sebum production. J Invest Dermatol 126:2002–2009PubMedCrossRefGoogle Scholar
  16. 16.
    Winston MH, Shalita AR (1991) Acne vulgaris. Pathogenesis and treatment. Pediatr Clin North Am 38(4):889–903PubMedGoogle Scholar
  17. 17.
    Zouboulis CC, Xia L, Detmar M et al (1991) Culture of human sebocytes and markers of sebocytic differentiation in vitro. Skin Pharmacol 4:74–83PubMedCrossRefGoogle Scholar
  18. 18.
    Zouboulis CC (2004) Acne and sebaceous gland function. Clin Dermatol 22:360–366PubMedCrossRefGoogle Scholar
  19. 19.
    Zouboulis CC, Böhm M (2004) Neuroendocrine regulation of sebocytes—a pathogenetic link between stress and acne. Exp Dermatol 13:31–35PubMedCrossRefGoogle Scholar
  20. 20.
    Zouboulis CC et al (2002) Corticotropin releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes. Proc Natl Acad Sci USA 99:7148–7153PubMedCrossRefGoogle Scholar
  21. 21.
    Zouboulis CC et al (1998) The human sebocyte culture model provides new insights into development and management of seborrhea and acne. Dermatology 196:21–31PubMedCrossRefGoogle Scholar
  22. 22.
    Zouboulis CC, Piquero-Martin J (2003) Update and future of systemic acne treatment. Dermatology 206:37–53PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Weon Ju Lee
    • 1
    Email author
  • Hong Dae Jung
    • 1
  • Hyun Joo Lee
    • 1
  • Byung Soo Kim
    • 1
  • Seok-Jong Lee
    • 1
  • Do Won Kim
    • 1
  1. 1.Department of DermatologyKyungpook National University School of MedicineDaeguRepublic of Korea

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