| Enhanced interleukin-10 signaling with 14-member macrolides in lipopolysaccharide-stimulated macrophages | |
Abstract/OtherAbstract
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Immunomodulatory 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. |
Authors
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Yamauchi, Keiko, Ishikawa, Tomomi, Shibata, Yoko, Abe, Shuichi, Inoue, Sumito, Takabatake, Noriaki, Kubota, Isao |
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Contributors
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Publication Detail
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Publisher : - Type : Text, article Format : - |
Date Detail
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2008-10-21, 2008-10-21, 2008-10-21 |
Subject
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interleukin-10, immunomodulatory effects, erythromycin, clarithromycin, STAT3, SOCS-3, macrophage, 610 |
Coverage
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Relation
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Excli Journal, 7 |
Source
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Copyright Information
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Other Details
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Languages : en |
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