title: Sulfur compounds block MCP-1 production by Mycoplasma fermentans-infected macrophages through NF-κB inhibition.
abstract: OBJECTIVE
  Hydrogen sulfide (H2S), together with nitric oxide (NO) and carbon monoxide (CO), belongs to a family of endogenous signaling mediators termed "gasotransmitters". Recent studies suggest that H2S modulates many cellular processes and it has been recognized to play a central role in inflammation, in the cardiovascular and nervous systems. By infecting monocytes/macrophages with Mycoplasma fermentans (M.F.), a well-known pro-inflammatory agent, we evaluated the effects of H2S.
  
  
  METHODS
  M.F.-infected cells were analyzed by ELISA and real time RT-PCR to detect the M.F. effects on MCP-1 and on MMP-12 expression. The role of two different H2S donors (NaHS and GYY4137) on MF-infected cells was determined by treating infected cells with H2S and then testing the culture supernatants for MCP-1 and on MMP-12 production by ELISA assay. In order to identify the pathway/s mediating H2S- anti-inflammatory activity, cells were also treated with specific pharmaceutical inhibitors. Cytoplasmic and nuclear accumulation of NF-κB heterodimers was analyzed.
  
  
  RESULTS
  We show that H2S was able to reduce the production of pro-inflammatory cytokine MCP-1, that was induced in monocytes/macrophages during M.F. infection. Moreover, MCP-1 was induced by M.F. through Toll-like receptor (TLR)-mediated nuclear factor-κB (NF-κB) activation, as demonstrated by the fact that TLR inhibitors TIRAP and MyD88 and NF-κB inhibitor IKK were able to block the cytokine production. In contrast H2S treatment of M.F. infected macrophages reduced nuclear accumulation of NF-κB heterodimer p65/p52.
  
  
  CONCLUSIONS
  Our data demonstrate that under the present conditions H2S is effective in reducing Mycoplasma-induced inflammation by targeting the NF-κB pathway. This supports further studies for possible clinical applications.
authors.forename: Francesca
authors.initials: F
authors.lastname: Benedetti
authors.forename: Sergio
authors.initials: S
authors.lastname: Davinelli
authors.forename: Selvi
authors.initials: S
authors.lastname: Krishnan
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gallo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scapagnini
authors.forename: Davide
authors.initials: D
authors.lastname: Zella
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. SCurreli@ihv.umaryland.edu.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Curreli
mesh_terms: D001483:Base Sequence; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D017931:DNA Primers; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology*; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis; D016858:Mycoplasma fermentans / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D060888:Real-Time Polymerase Chain Reaction; D020298:U937 Cells
chemical_list: D018932:Chemokine CCL2; D017931:DNA Primers; D016328:NF-kappa B; D053508:Matrix Metalloproteinase 12; D006862:Hydrogen Sulfide