isolation-culture-characterization-primary-schwann-cells

Isolation, Culture, and Characterization of Primary Schwann Cells, Keratinocytes, and Fibroblasts from Human Foreskin

This protocol describes isolation methods, culturing conditions, and characterization of human primary cells with high yield and viability using rapid ...

The Pennsylvania State University College of Medicine

Isotretinoin (13-cis retinoic acid (13-cis RA)) is the most potent inhibitor of sebum production, a key component in the pathophysiology of acne, yet its mechanism of action remains largely unknown. The effects of 13-cis RA, 9-cis retinoic acid (9-cis RA), and all-trans retinoic acid (ATRA) on cell proliferation, apoptosis, and cell cycle proteins were examined in SEB-1 sebocytes and keratinocytes. 13-cis RA causes significant dose-dependent and time-dependent decreases in viable SEB-1 sebocytes. A portion of this decrease can be attributed to cell cycle arrest as evidenced by decreased DNA synthesis, increased p21 protein expression, and decreased cyclin D1. Although not previously demonstrated in sebocytes, we report that 13-cis RA induces apoptosis in SEB-1 sebocytes as shown by increased Annexin V-FITC staining, increased TUNEL staining, and increased cleaved caspase 3 protein. Furthermore, the ability of 13-cis RA to induce apoptosis cannot be recapitulated by 9-cis RA or ATRA, and it is not inhibited by the presence of a retinoid acid receptor (RAR) pan-antagonist AGN 193109. Taken together these data indicate that 13-cis RA causes cell cycle arrest and induces apoptosis in SEB-1 sebocytes by a RAR-independent mechanism, which contributes to its sebosuppressive effect and the resolution of acne.

13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes.

Acne vulgaris is a common skin condition seen by physicians. It primarily affects adolescents, but can continue into adulthood. A key factor in the pathogenesis of acne is sebum production. Typical therapy includes combinations of topical retinoids and antimicrobials for mild acne, with the addition of oral antibiotics for moderate to severe disease. In the most recalcitrant cases or for nodulocystic acne, oral retinoids are indicated. In women who fail to respond to conventional treatment, hormonal therapy is often used adjunctively. Only isotretinoin and hormonal therapy improve acne via their action on the sebaceous glands. This article focuses on the mechanisms by which these treatment modalities act on the sebaceous glands and their clinical use in the practice of medicine.

Pharmacologic modulation of sebaceous gland activity: mechanisms and clinical applications.

Retinoids are used in the treatment of inflammatory skin diseases and malignancies, but studies characterizing the in vivo actions of these drugs in humans are lacking. Isotretinoin is a pro-drug for all-trans retinoic acid, which can induce long-term remissions of acne; however, its complete mechanism of action is unknown. We hypothesized that isotretinoin induces remission of acne by normalizing the innate immune response to the commensal bacterium Propionibacterium acnes. Compared with normal subjects, peripheral blood monocytes from acne patients expressed significantly higher levels of Toll-like receptor 2 (TLR-2) and exhibited significantly greater induction of TLR-2 expression following P. acnes stimulation. Treatment of patients with isotretinoin significantly decreased monocyte TLR-2 expression and subsequent inflammatory cytokine response to P. acnes after 1 week of therapy. This effect was sustained 6 months following cessation of therapy, indicating that TLR-2 modulation may be involved in the durable therapeutic response to isotretinoin. This study demonstrates that isotretinoin exerts immunomodulatory effects in patients and sheds light on a potential mechanism for its long-term effects on acne. The modulation of TLR-2 expression on monocytes has important implications in other inflammatory disorders characterized by TLR-2 dysregulation.

Article	Year
13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. The Journal of investigative dermatology\| PubMed ID: 16575387	2006
Pharmacologic modulation of sebaceous gland activity: mechanisms and clinical applications. Dermatologic clinics\| PubMed ID: 17430751	2007
Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients. The Journal of investigative dermatology\| PubMed ID: 22513780	2012
Cross-sectional study reveals reduced odds of allergies in people with hidradenitis suppurativa. Journal of the American Academy of Dermatology\| PubMed ID: 32781187	2021

Amanda M. Nelson

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