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Human Keratinocytes: First Line of Defense

Keratinocytes are the major cell type of the epidermis (the outermost skin layer) and are also found in the oral mucosa. They form the primary protective barrier between the internal milieu and the external environment. Keratinocytes are so named because they produce high amounts of the protein keratin, a fibrous protein that composes the protective barrier of the skin and is also found in hair and nails. Keratinocytes are mitotically active in the inner layers of the epidermis. As they mature, keratinocytes migrate to the outer layer of the epidermis and become flattened, lose their nuclei, and fill with keratin. These terminally differentiated keratinocytes therefore form the skin’s first line of defense.

Keratinocytes are actively involved in homeostasis, and are the cell type in which psoriasis manifests. Additionally, oral keratinocytes, found in the oral mucosa, are particularly sensitive to bacterial infection and dysregulation of these cells from bacterial infection can lead to periodontal disease.

Recent Research Using Lifeline® Keratinocytes

Triclosan (TCS) is an antibacterial agent that is commonly used in some types of soap, mouthwash, detergents, and toothpaste. Although considered relatively safe for human use, it does accumulate in the environment, raising certain environmental concerns. However, studies are beginning to demonstrate that TCS does have certain effects on human cellular function, particularly in mast cells, white blood cells that are most well known for releasing histamine, a major player in the inflammatory response.

In a 2015 study, Weatherly et al. investigated the mechanism by which TCS affects mast cells and other cell types. They found that TCS inhibits ATP production by mast cells, NIH-3T3 fibroblasts, and Lifeline® primary human keratinocytes, grown in DermaLife K medium. Importantly, ATP is crucial for degranulation of mast cells, and the researchers demonstrate that TCS attenuates the degranulation process, and thus affects one of the most important functions of these cells. Together, this study demonstrates that TCS has clear effects on ATP production in mast cells, fibroblasts, and keratinocytes, and therefore, could affect additional cell types within the body and organisms within the environment.

Psoriasis is a skin condition caused by hyperproliferation of epithelial keratinocytes and an increased inflammatory environment. In a 2015 study, Bai et al. set out to discover whether the Wnt signaling pathway was involved in the pathogenesis of psoriasis. They found that SFRP4, a Wnt signaling negative regulator, was decreased in psoriatic lesions in mice with a psoriasis-like condition, as well as in human patients. Using Lifeline® normal human epithelial keratinocytes, the group found that exogenous SFRP4 decreased proliferation, suggesting that its lower expression in psoriatic lesions may lead to keratinocyte hyperproliferation.

In a mouse model of psoriasis, a Wnt inhibitor also decreased proliferation. Additionally, the researchers found that treatment of psoriatic lesions in mice with SFRP4 improved lesion severity. Finally, the researchers found that the mechanism of SFRP4 downregulation in psoriasis is increased promoter methylation. Together, the results of this study suggest that SFRP4 downregulation by promoter methylation in psoriasis contributes to pathogenesis by increasing epidermal keratinocyte proliferation.

New! Lifeline® Oral Keratinocytes

Lifeline® has now introduced oral keratinocytes (gingiva). These cells abolish the need to have access to primary human tissue or perform cell isolations from primary tissue. Lifeline® oral keratinocytes are optimized for growth in DermaLife K medium. In fact, researchers have already been using DermaLife medium to isolate and culture oral keratinocytes as described below.

Porphyromonas gingivalis is a bacterial pathogen that plays a pathogenic role in periodontal disease. Zhou et al. showed that infection of oral epithelial cells grown in DermaLife K medium, with P. gingivalis caused b-catenin proteolysis. Additionally, the researchers found functionally active b-catenin fragments in the nucleus following infection. The results from this study suggest that P. gingivalis infection can cause potential non-canonical activation of the Wnt pathway.

Wang et al. also studied the effects of P. gingivalis on gingival epithelial cells grown in DermaLife K medium. They found that P. gingivalis infection increases reactive oxygen species, which in turn, activate FOXO signaling. FOXO family transcription factors induce cellular signals that include oxidative stress protection and survival, identifying this pathway as an important cellular response to P. gingivalis infection.

Bhattacharya et al. investigated the role P. gingivalis and Fusobacterium nucleatum may play in delaying would healing following infection. They used primary oral keratinocytes, grown in DermaLife medium, and found that in an in vitro scratch assay, P. gingivalis and F. nucleatum (although with less effect) delayed wound healing. This was associated with less proliferation, increased apoptosis, and impaired migration. Together, the results of this study suggest that P. gingivalis (primarily) negatively affects wound healing, potentially increasing its pathogenic capacity.

Moffatt et al. set out to discover whether Filifactor alocis was a periodontal pathogen. Indeed, they found that F. alocis associated with primary gingival epithelial cells grown in DermaLife medium. Additionally, they found that F. alocis infection stimulated secretion of pro-inflammatory cytokines, including IL-1b and TNF-a. Finally, they demonstrate that F. alocis infection induces apoptosis and decreases MEK activation. Together, this study suggests that F. alocis fits the profile of a periodontal pathogen and may contribute to periodontal disease.

Lifeline® Keratinocytes for Your Research Needs

 Lifeline® keratinocytes, optimized for growth in DermaLife K medium, include:

Let us know how you are using Lifeline® cells or media to answer your scientific questions and your study could be featured here on our blog!

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