ArticlePloS one2017
TLR4 as a negative regulator of keratinocyte proliferation.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- TLR4-paxillin-Rac1 signaling mediates LPS-induced dysregulation of keratinocyte function.iScience · 2026Article
- Oral microbiota-driven immune modulation along the oral-gut axis: from local signals to systemic inflammation.NPJ biofilms and microbiomes · 2026Review
- Infection-driven proliferative phase impairment in chronic wounds: a mechanistic framework for precision regenerative therapy.Frontiers in immunology · 2026Review
- From actinic keratosis to cutaneous squamous cell carcinoma: the key pathogenesis and treatments.Frontiers in immunology · 2025Review
- The Secretion of Inflammatory Cytokines Triggered by TLR2 Through Calcium-Dependent and Calcium-Independent Pathways in Keratinocytes.Mediators of inflammation · 2024Article
- Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model.International journal of molecular sciences · 2022Article
- Matrix Effectors in the Pathogenesis of Keratinocyte-Derived Carcinomas.Frontiers in medicine · 2022Review
- Investigating Cutaneous Squamous Cell CarcinomaFrontiers in medicine · 2022Review
- A Single-Step Genome Wide Association Study on Body Size Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs.Frontiers in genetics · 2021Article
- TLR5: A prognostic and monitoring indicator for triple-negative breast cancer.Cell death & disease · 2019Article
- TLR4 in skin cancer: From molecular mechanisms to clinical interventions.Molecular carcinogenesis · 2019Article
- The Mechanism of CIRP in Regulation of STAT3 Phosphorylation and Bag-1/S Expression Upon UVB Radiation.Photochemistry and photobiology · 2018Article
- Pharmacological TLR4 Antagonism Using Topical Resatorvid Blocks Solar UV-Induced Skin Tumorigenesis in SKH-1 Mice.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- Aberrant miR-219-5p is correlated with TLR4 and serves as a novel biomarker in patients with multiple organ dysfunction syndrome caused by acute paraquat poisoning.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC) of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro. In addition, subcutaneously injected HaCaT keratinocytes with shTLR4 formed growing tumors in nude mice. In contrast, we observed lower proliferation and increased migration in vitro of the SCC13 cell line stably overexpressing TLR4 in comparison to SCC13 TLR4 negative cells. In vivo, SCC13 TLR4-overexpressing tumors showed delayed growth in comparison to TLR4 negative tumors. The overexpression of TLR4 in SCC13 tumor cells was followed by phosphorylation of ERK1/2 and JNK and increased expression of ATF3. In gene expression arrays, the overexpression of TLR4 in tumor cells correlated with gene expression of ATF-3, IL-6, CDH13, CXCL-1 and TFPI. In summary, TLR4 negatively regulates the proliferation of keratinocytes and its overexpression reduces tumor growth of SCC cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.