ABSTRACT
This study was designed to investigate the effect of exogenous hydrogen sulfide (H2S) on the secretion of Heme oxygenase (HO-1) and proinflammatory cytokines in human mononuclear cell line THP-1 stimulated by lipid-associated membrane proteins (LAMPs) prepared from Mycoplasma pneumoniae (M. pneumoniae) and explore its regulatory mechanism. Cultured cells were stimulated with M. pneumoniae LAMPs after pretreatment with H2S to analyze the production of proinflammatory cytokines and HO-1 by enzyme-linked immunosorbent assay (ELISA) and Western blot. The results showed that THP-1 cells, which were stimulated by LAMPs after pretreatment with H2S, had decreased production of interleukin-6 (IL-6) and interleukin-8 (IL-8) by inhibiting the mitogen-activated protein kinases (MAPKs)/nuclear factor-kappa B (NF-κB) signaling pathway and increased expression of HO-1 by activating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Our results indicate that H2S may play an important role in attenuating inflammation induced by M. pneumoniae LAMPs due to its ability to decrease the production of IL-6 and IL-8 and increase the expression of the HO-1. These findings support further studies for possible clinical applications.
Subject(s)
Cytokines/biosynthesis , Heme Oxygenase-1/biosynthesis , Hydrogen Sulfide/pharmacology , Lysosomal Membrane Proteins/metabolism , Mycoplasma pneumoniae/metabolism , THP-1 Cells/metabolism , Cytokines/antagonists & inhibitors , Cytokines/genetics , Gene Expression Regulation, Enzymologic , Heme Oxygenase-1/genetics , Humans , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Lysosomal Membrane Proteins/antagonists & inhibitors , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/metabolism , Mycoplasma pneumoniae/drug effects , THP-1 Cells/drug effectsABSTRACT
A series of inflammatory responses caused by Mycoplasma pneumoniae largely depend on the lipid-associated membrane proteins (LAMPs). Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, is considered to be a critical modulator of inflammatory responses and cellular redox homeostasis. Monocytes play an important role in the invasion and immunity to resist pathogens. Here, we investigated the role of Nrf2 in the anti-inflammatory response stimulated by LAMPs using the human monocyte cell line THP-1. LAMPs were shown to affect the localization of Nrf2, and the levels of reactive oxygen species and inflammatory reactants, including nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines (IL-6, IL-8), were highly elevated in LAMP-stimulated Nrf2-silenced THP-1 cells. Moreover, LAMPs induced the levels of mRNA and the expression of heme oxygenase-1 (HO-1). In summary, our results demonstrated that LAMPs cause nuclear translocation of Nrf2, which further suppresses the expression of inflammatory reactants in THP-1 cells.
