Toxic Antiseptic Agents and Searching for New Treatments for Psoriasis
Anatomy of the Skin, the Body’s Largest Organ
The skin is the largest organ in the human body and is the largest area in contact with the external environment. In addition to providing physical protection, the skin also regulates body temperature and provides sensory information. As a result, it must be resilient enough to survive these challenges to homeostasis. The epidermis is the tough outer layer of the skin that is largely comprised of keratinocytes, which are continuously shed. The epidermis also contains melanocytes, the pigmented cells of the skin, which are also the cell-of-origin for melanoma, a type of skin cancer. The dermis is the layer below the epidermis and contains among other cell types, fibroblasts, which produce extracellular matrix structural proteins like collagen. The dermis is also the site of the hair follicles and sweat glands. Finally, the subcutaneous layer, or hypodermis, serves to attach dermis and epidermis to underlying structures like bone and muscle.
The Lifeline® catalog contains the following cell systems for studying the skin:
- Epidermal melanocytes (adult and neonatal)
- Epidermal keratinocytes (adult, neonatal, and 10-donor pool)
- Dermal microvascular endothelial cells (adult and neonatal)
- Dermal fibroblasts (adult and neonatal)
Lifeline® Skin Cells in Recent Research
Heavy use of antiseptics by healthcare workers may lead to skin conditions like dermatitis, due to inclusion of certain biocides as ingredients. Biocides are designed to kill microscopic pathogens, like bacteria, but may also have adverse side effects on skin cells. In a previous study, the research group led by H. Nagamune synthesized two new bis-quarternary ammonium compounds, 3PHBO-12 and 3HHDMP-12, that showed promising bactericidal activity with low associated cytotoxicity against normal human epidermal keratinocytes (NHEKs). To further characterize these compounds and compare them to conventional antiseptic biocide compounds, they tested the cytotoxicity of the compounds to determine whether they could affect cell proliferation.
In this new study, the authors used Lifeline® NHEKs and adult normal human dermal fibroblasts, as well as the THP-1 monocytic and HL-60 human leukemia cell lines. They found that in all cell lines tested, their new compounds, 3PHBO-12 and 3HHDMP-12 were less cytotoxic than octenidine dihydrochloride (OCT) and benzalkonium chloride (BAC), two commonly used biocidal compounds. However, the cytotoxicity of 3PHBO-12 and 3HHDMP-12 was still greater than that of the biguanide-based compounds tested, hlorhexidine digluconate (CHG) and polyhexamethylenebiguanide (PHMB).
Next, the authors evaluated whether these compounds could induce mRNA expression of the inflammatory cytokine IL1A in NHEKs. Although OCT, BAC, and 3PHBO-12 induced IL1A at the concentrations used, 3HHDMP-12 treatment did not alter IL1A expression. Using a 3D in vitro model of the epidermis, the authors then demonstrated that treatment with BAC and OCT, but not 3PHBO-12, 3HHDMP-12, or other commonly used biocides, reduced cell viability. Finally, the authors examined whether treatment with various biocidal compounds influenced additional inflammatory cytokine production and secretion using the 3D in vitro epidermis model. Using RT-PCR to measure gene expression, they found that OCT and BAC treatment induced mRNA expression of IL1A, IL1B, and TNFA; BAC treatment also induced IL8 expression. Finally, using ELISA, the authors measured secretion of the inflammatory mediators IL-1α and TNF-α and found that IL-1α secretion increased following treatment with OCT and BAC; neither 3PHBO-12 and 3HHDMP-12 significantly affected IL-1α and TNF-α secretion.
Together, the results of this study suggest that 3PHBO-12 and 3HHDMP-12 are similarly or less cytotoxic than certain other commonly used antiseptic biocides and are likely safe for use as antiseptic agents.
Psoriasis is an inflammatory condition exhibited by red patches on the skin due to excessive proliferation of keratinocytes. The disease is also associated with increased low-density lipoprotein (LDL), which is often referred to as “bad cholesterol.” In a 2018 study, Luan and colleagues set out to determine whether targeting PCSK9, an enzyme that increases circulating LDL levels by regulating levels of the LDL receptor, could be used as a topical therapy for psoriasis.
First, the researchers examined PCSK9 expression in human psoriasis samples, as well as in psoriatic lesions (induced using imiquimod) from Pcsk9 knockout mice or mice treated with anti-Pcsk9 siRNA. Importantly, the authors found that PCSK9 expression was upregulated in psoriatic lesions. Additionally, they found that loss of Pcsk9 activity decreased the inflammatory response to imiquimod and reduced keratinocyte hyperproliferation.
Finally, using Lifeline® human keratinocytes, the researchers found that suppression of PCSK9 causes cell cycle dysregulation and apoptosis. Together, their results suggest that PCSK9 plays a pro-inflammatory role in psoriasis and topical siRNA-mediated anti-PCSK9 therapy could be a novel treatment approach for patients with psoriasis.
Check in with us here on the blog to see how researchers worldwide use our cell systems. If you have published a study using our cell systems, let us know and it could be the next feature!