Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages

dc.contributor.authorAbe, Shuichi
dc.contributor.authorInoue, Sumito
dc.contributor.authorIshikawa, Tomomi
dc.contributor.authorKubota, Isao
dc.contributor.authorShibata, Yoko
dc.contributor.authorTakabatake, Noriaki
dc.contributor.authorYamauchi, Keiko
dc.date.accessioned2008-10-21T12:42:53Z
dc.date.available2008-10-21T12:42:53Z
dc.date.issued2008-10-21T12:42:53Z
dc.description.abstractImmunomodulatory effects of 14-member macrolides, namely erythromycin (EM) and clarithromycin (CAM), have been reported in chronic respiratory infectious diseases. It has been suggested that 14-member macrolides have immunomodulatory effects on various lung cells such as alveolar macrophages. Interleukin (IL)-10 is an immunomodulatory cytokine that performs an irreplaceable role in negatively regulating inflammation, primarily via a mechanism that selectively blocks the expression of pro-inflammatory genes. It activates sig-nal transducer and activator of transcription (STAT)-3, and subsequently induces the suppres-sor of cytokine signaling-3 (SOCS-3), resulting in the resolution of inflammatory response in macrophages. However, it has been still unclear whether 14-member macrolides exert immu-nomodulatory effects via IL-10 signaling pathway. We aimed to evaluate whether 14-member macrolides affect the IL-10 signaling pathway. The RAW264.7 macrophage cell line was pre-treated with EM or CAM, and stimulated with lipopolysaccharide (LPS). The levels of IL-10, IL-10 receptor, phosphorylated (p) STAT-3, and SOCS-3 were determined by RT-PCR, ELISA and immunoblotting. We observed increased levels of IL-10, p-STAT-3 and SOCS-3 in the treated cells. In addition, while the levels of tumor necrosis factor-α 6 h after LPS stimulation was equal between vehicle-treated and CAM-treated macrophage cells, those of CAM-treated cells were repressed 36 h following LPS stimulation, compared with those of the control cells. Therefore, the 14-member macrolides may initiate an early resolution of inflammation, in part, via the enhancement of the IL-10/STAT-3/SOCS-3 pathway.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/25810
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-576
dc.language.isoende
dc.relation.ispartofseriesEXCLI Journal ; Vol. 7, 2008en
dc.subjectclarithromycinen
dc.subjecterythromycinen
dc.subjectimmunomodulatory effectsen
dc.subjectinterleukin-10de
dc.subjectmacrophageen
dc.subjectSOCS-3de
dc.subjectSTAT3de
dc.subject.ddc610
dc.titleEnhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophagesen
dc.typeTextde
dc.type.publicationtypearticleen
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1

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