Abstract
Background and aimsHydrogen 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.MethodsM.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.ResultsWe 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.ConclusionsOur 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.
Highlights
Background and aimsHydrogen sulfide (H2S), together with nitric oxide (NO) and carbon monoxide (CO), belongs to a family of endogenous signaling mediators termed “gasotransmitters”
Mycoplasma infection induces Monocyte Chemoattractant Protein-1 (MCP-1) in U937 cells and in human monocyte-derived macrophages The induction of pro-inflammatory cytokines is a hallmark of M.F.-mediated inflammatory activity [22]
According to these results and to the role played by MCP-1 in inflammation [39], we focused our studies on this chemokine
Summary
Hydrogen sulfide (H2S), together with nitric oxide (NO) and carbon monoxide (CO), belongs to a family of endogenous signaling mediators termed “gasotransmitters”. The precise role of H2S in inflammation is still far from clear: it may have pro- or anti- inflammatory effects under different conditions [11]. H2S inhibits the activation of the transcription factor nuclear factor-κB (NF-κB), essential for the activation of most pro-inflammatory genes, in murine macrophages RAW264.7 cell line following exposure to bacterial endotoxin and blocks the increase of inducible nitric oxide synthase (iNOS) expression and NO production [13]. H2S inhibits endotoxin-induced upregulation of iNOS expression, NO production and TNF-α expression in cultured microglia These effects were attributed at least in part to the suppression by H2S of endotoxin-induced p38 mitogen-activated protein (MAP) kinase phosphorylation [16]. H2S increases NO production with consequential down-regulation of the pro-angiogenic cytokine VEGF (vascular endothelial growth factor) in human keratinocytes [20]
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