Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species.
The innate immune response is critical for the epithelial antimicrobial barrier. The human beta-defensins are small, cationic antimicrobial peptides that are made by epithelial cells and that play a role in mucosal and skin defenses. Human beta-defensin 1 (hBD-1) is expressed constitutively in epithelial tissues, whereas hBD-2 and hBD-3 are expressed in response to bacterial stimuli or inflammation. Previous studies showed that hBD-2 was induced by Fusobacterium nucleatum cell wall extract without the involvement of the NF-kappaB transcription factors, which typically are associated with innate immunity and inflammation. The goal of this study was to characterize signaling pathways involved in hBD-2 induction in response to commensal and pathogenic bacteria. Cultured human oral and foreskin keratinocytes were treated separately with inhibitors of NF-kappaB, c-Jun N-terminal kinase (JNK), and p38 and then stimulated with oral commensal Streptococcus gordonii, oral pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, skin commensal Staphylococcus epidermidis, or skin pathogen Streptococcus pyogenes. Different bacteria induced different levels of hBD-2 and in response to the various inhibitors tested, although certain common patterns were observed for commensal- and pathogen-stimulated cells. hBD-2 induction by all bacteria tested was partially or completely blocked by inhibitors of the JNK and p38 pathways. However, in addition, hBD-2 induction by pathogenic bacteria in both oral and foreskin keratinocytes was blocked by inhibitors of NF-kappaB. The results indicate that commensal and pathogenic bacteria utilize different pathways in hBD-2 induction and suggest that epithelial cells from different body sites have common signaling mechanisms to distinguish between commensal and pathogenic bacteria.
Chung
Whasun O
WO
Department of Oral Biology, University of Washington, Seattle, Washington 98195-7132, USA. sochung@u.washington.edu
Dale
Beverly A
BA
D001419:Bacteria / Q000276:immunology / Q000472:pathogenicity*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D005881:Gingiva / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D048031:JNK Mitogen-Activated Protein Kinases; D015603:Keratinocytes / Q000276:immunology* / Q000382:microbiology; D048670:MAP Kinase Kinase 4; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
C106641:DEFB4A protein, human; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D023083:beta-Defensins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases