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Sulfur compounds block MCP-1 production by Mycoplasma fermentans-infected macrophages through NF-κB inhibition

BACKGROUND AND AIMS: Hydrogen sulfide (H(2)S), together with nitric oxide (NO) and carbon monoxide (CO), belongs to a family of endogenous signaling mediators termed “gasotransmitters”. Recent studies suggest that H(2)S modulates many cellular processes and it has been recognized to play a central r...

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Detalles Bibliográficos
Autores principales: Benedetti, Francesca, Davinelli, Sergio, Krishnan, Selvi, Gallo, Robert C, Scapagnini, Giovanni, Zella, Davide, Curreli, Sabrina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046042/
https://www.ncbi.nlm.nih.gov/pubmed/24886588
http://dx.doi.org/10.1186/1479-5876-12-145
Descripción
Sumario:BACKGROUND AND AIMS: Hydrogen sulfide (H(2)S), together with nitric oxide (NO) and carbon monoxide (CO), belongs to a family of endogenous signaling mediators termed “gasotransmitters”. Recent studies suggest that H(2)S 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 H(2)S. 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 H(2)S donors (NaHS and GYY4137) on MF-infected cells was determined by treating infected cells with H(2)S 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 H(2)S- 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 H(2)S 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 H(2)S treatment of M.F. infected macrophages reduced nuclear accumulation of NF-κB heterodimer p65/p52. CONCLUSIONS: Our data demonstrate that under the present conditions H(2)S is effective in reducing Mycoplasma-induced inflammation by targeting the NF-κB pathway. This supports further studies for possible clinical applications.