title: Lipopolysaccharide and IL-1β coordinate a synergy on cytokine production by upregulating MyD88 expression in human gingival fibroblasts.
abstract: Both lipopolysaccharide (LPS) and interleukin (IL)-1β activate the MyD88-dependent signaling pathways to stimulate proinflammatory cytokine expression. However, it remains unknown how LPS and IL-1β interact with each other to coordinate the stimulation. In this study, we sought to investigate the interaction between LPS and IL-1β on MyD88-dependent signaling pathways in human gingival fibroblasts (HGFs). Results showed that LPS derived from Porphyromonas gingivalis (Pg LPS) and IL-1β cooperatively stimulated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) signaling pathways, and subsequent expression of proinflammatory cytokine expression. Furthermore, our results showed that Pg LPS and IL-1β exerted a synergy on MyD88 expression and knockdown of MyD88 expression by small interfering RNA diminished the synergistic effect of Pg LPS and IL-1β on IL-6 expression, suggesting that upregulation of MyD88 is involved in the coordinated stimulation by Pg LPS and IL-1β of proinflammatory cytokine expression. Finally, our results showed that pharmacological inhibitors for MAPK and NFκB significantly reduced IL-6 secretion stimulated by Pg LPS and IL-1β, indicating that the MyD88-dependent MAPK and NFκB signaling pathways are essential for the upregulation of proinflammatory cytokine expression by Pg LPS and IL-1β. Taken together, this study showed that LPS and IL-1β coordinate a synergy on cytokine production by upregulating MyD88 expression in HGFs.
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States.
authors.forename: Colleen W
authors.initials: CW
authors.lastname: Brinson
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, United States.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, United States. Electronic address: huangyan@musc.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D016866:Bacteroidaceae Infections / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005881:Gingiva / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016966:Porphyromonas gingivalis / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B
keywords: Inflammation; Interleukin-1 beta; Lipopolysaccharide; MyD88