Lipopolysaccharide and IL-1β coordinate a synergy on cytokine production by upregulating MyD88 expression in human gingival fibroblasts

Both lipopolysaccharide (LPS) and interleukin (IL)-1 beta activate the MyD88-dependent signaling pathways to stimulate proinflammatory cytokine expression. However, it remains unknown how LPS and IL -1 beta interact with each other to coordinate the stimulation. In this study, we sought to investigate the interaction between LPS and IL -1 beta on MyD88-dependent signaling pathways in human gingival fibroblasts (HGFs). Results showed that LPS derived from Porphyromonas gingivalis (Pg LPS) and IL -1 beta cooperatively stimulated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF kappa B) signaling pathways, and subsequent expression of proinflammatory cytokine expression. Furthermore, our results showed that Pg LPS and IL -1 beta exerted a synergy on MyD88 expression and knockdown of MyD88 expression by small interfering RNA diminished the synergistic effect of Pg LPS and IL -1 beta on 1L-6 expression, suggesting that upregulation of MyD88 is involved in the coordinated stimulation by Pg LPS and IL -1 beta of proinflammatory cytokine expression. Finally, our results showed that pharmacological inhibitors for MAPK and NF kappa B significantly reduced IL-6 secretion stimulated by Pg LPS and IL -1 beta, indicating that the MyD88-dependent MAPK and NF kappa B signaling pathways are essential for the upregulation of proinflammatory cytokine expression by Pg LPS and IL -1 beta. Taken together, this study showed that LPS and IL -1 beta coordinate a synergy on cytokine production by upregulating MyD88 expression in HGFs. Published by Elsevier Ltd.