Abstract
Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from Ishige okamuarae, a brown alga. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that DPHC strongly reduces the production of interleukin 6 (IL-6), but not that of tumor necrosis factor-alpha (TNF-α) induced by LPS. DPHC (12.5 and 100 μM) suppressed the phosphorylation and the nuclear translocation of NF-kappaB (NF-κB), a central signaling molecule in the inflammation process induced by LPS. The suppressor of cytokine signaling 1 (SOCS1) is a negative feedback regulator of Janus kinase (Jak)-signal transducer and activator of transcription (STAT) signaling. In this study, DPHC inhibited STAT5 expression and upregulated that of SOCS1 at a concentration of 100 μM. Furthermore, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK) (a specific NF-κB inhibitor) and JI (a specific Jak2 inhibitor) reduced the production of IL-6, but not that of tumor necrosis factor-alpha (TNF-α) in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that DPHC inhibits IL-6 production via the downregulation of NF-κB and Jak2-STAT5 pathway and upregulation of SOCS1.
Highlights
Inflammation is an important body defense mechanism against pathogens and diverse external stimuli
interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) are representative pro-inflammatory cytokines generated by external stimuli in macrophages
To assess DPHC for its anti-inflammatory effect, we investigated the inhibitory activity of DPHC on LPS-induced IL-6 and TNF-α production, important pro-inflammatory cytokines, in
Summary
Inflammation is an important body defense mechanism against pathogens and diverse external stimuli. Numerous endogenous inflammatory mediators, including cytokines, chemokines, prostaglandins and nitric oxide (NO), are present in the body. LPS, an inducer of innate immune response, binds to a myeloid differentiation factor-2 (MD-2)/TLR4 complex, initiates the downstream signaling pathway and releases various inflammatory chemokines and cytokines, including IL-6, inducible nitric oxide synthase (iNOS) and TNF-α [6,7,8]. The Janus kinase (Jak) pathway is triggered by various ligands, including cytokines, and it activates immune and inflammatory responses, as well as other cellular events [13,14]. We investigated the activity and action mechanism of DPHC on the production of IL-6, a pivotal cytokine of the inflammatory process in LPS-stimulated RAW264.7 cells
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