Antimicrobial-protein-S100A15-induction by microbial pathogens in oral cells mediated by ASK1-JNK/p38-NF-kB-pathways

Objectives: Although the identification of S100A15 protein as a novel antimicrobial protein in cutaneous tissues, its induction and regulation by microbial pathogens, in oral mucosa derived cells are currently unknown.

Methods: Real Time PCR (RT-PCR), Western blot analysis, in vitro kinase assay and electrophoretic mobility shift assay (EMSA).

Results: Stimulation of primary gingival fibroblasts (GF) and KB cell line with either microbial pathogens or their highly purified major cell wall constituents, lipopolysaccharids (LPS) and lipoteichoic acids (LTA) led to the induction of S100A15 gene transcription, the activation of apoptosis-signal regulating kinase 1 (ASK1), c-Jun-N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK), kinase of NF-kB inhibitor (IKK-a), and the transcription factors NF-kB, AP-1, ATF-2 and ELK-1. However, inhibitor experiments provided evidence for the modulation of LPS/LTA induced S100A15 gene transcription by Toll-like receptor 4 (e.g. LPS) or Toll-like receptor 2 (e.g. LTA) via ASK1-JNK/p38 and NF-kB pathways.

Conclusion: Our data demonstrated for the first time the induction of S100A15 expression by LPS/LTA in oral mucosa derived cells via molecular mechanisms including ASK1-JNK/p38 and NF-kB pathways.