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DOI: 10.1055/s-0035-1565480
Anti-inflammatory effect of streptochlorin via TRIF-dependent signaling pathways in cellular and mouse models
Streptochlorin, a small compound derived from marine actinomycete, has been shown to have anti-angiogenic, anti-tumor, and anti-allergic activities. However, the anti-inflammatory effects and underlying mechanisms have not yet been reported. In the present study, we investigated the effect of streptochlorin on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. As shown in Fig. 1, streptochlorin attenuated the production of proinflammatory mediators such as nitric oxide, cyclooxygenase-2, pro-interleukin (IL)-1β, and IL-6 in LPS-stimulated RAW264.7 cells through inhibition of the Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling pathway. IC50 to inhibit those inflammatory mediators is 25 µM.
To verify the in vivo efficacy of streptochlorin, we injected 0.11˜1.1 mg/kg of streptochlorin by intra peritoneal injection in mouse (Fig. 2). Streptochlorin suppressed the infiltration of immune cells such as neutrophils into the lung and proinflammatory cytokine production such as IL-6 and TNF-α in broncho-alveolar lavage fluid (BALF) in the LPS-induced acute lung injury (ALI) mouse model.
Taken together, streptochlorin has potent anti-inflammatory effects through regulating TRIF-dependent signaling pathways, suggesting that streptochlorin may provide a valuable therapeutic strategy in treating various inflammatory diseases.