Document Type
Article
Publication Date
3-10-2023
Publication Title
International Journal of Molecular Sciences
Abstract
The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram− or gram+ bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either gram− or gram+ bacterial pathogens or their purified membrane components (LPS and LTA) results in the activation of NF-κB, apoptosis-regulating kinase1 (ASK1), and MAP kinase signaling pathways including, c-Jun N-terminal kinase (JNK) and p38 together with their physiological substrates AP-1 and ATF-2, respectively. Inhibition of S100A15 by antibodies-mediated Toll-like receptor 4 (TLR4) or Toll-like receptor 2 (TLR2) neutralization reveals the induction of S100A15 protein by LPS/gram− bacterial pathogens to be TLR4- dependent mechanism, whereas induction by LTA/gram+ bacterial pathogens to be TLR2- dependent mechanism. Pre-treatment of GF and KB cells with JNK (SP600125), p38 (SB-203580), or NF-κB (Bay11-7082) specific inhibitors further demonstrates the importance of JNK, p38 and NF-κB pathways in the regulation of gram−/gram+ bacterial pathogen-induced S100A15 expression. Our data provide evidence that S100A15 is induced in cancer and non-cancer oral mucosa-derived cell lines by gram−/gram+ bacterial pathogens and provide insight into the molecular mechanisms by which gram− and gram+ bacterial pathogens induce S100A15 expression in the oral mucosa.
PubMed ID
36982421
Volume
24
Issue
6
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Selimovic, Denis; Kharouf, Naji; Carrouel, Florence; Hassan, Sofie Yasmin; Flanagan, Thomas W.; Hassan, Sarah Lilly; Megahed, Mosaad; Haikel, Youssef; Santourlidis, Simeon; and Hassan, Mohamed, "Induction of Antimicrobial Protein S100A15 Expression by Oral Microbial Pathogens Is Toll-like Receptors-Dependent Activation of c-Jun-N-Terminal Kinase (JNK), p38, and NF-κB Pathways" (2023). School of Medicine Faculty Publications. 850.
https://digitalscholar.lsuhsc.edu/som_facpubs/850
10.3390/ijms24065348
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File Size
1498 KB
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Amino Acids, Peptides, and Proteins Commons, Chemical Actions and Uses Commons, Medical Pharmacology Commons