International immunopharmacology
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Int. Immunopharmacol. · Sep 2011
Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-κB and AP-1 signaling pathways.
Angelica sinensis (AS), an herb used in traditional Chinese medicine, is thought to have anti-inflammatory activities. Ligustilide is its most abundant ingredient. This study sought to determine ligustilide's effects on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. ⋯ Ligustilide also inhibited the phosphorylation of IκB kinase (IKK) and mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). The intracellular reactive oxygen species (iROS) level was also significantly decreased. These results suggest that ligustilide exhibits anti-inflammatory activities by blocking the activation of MAPKs/IKK and the downstream transcription factors AP-1 and NF-κB, which may result from ligustilide's down-regulation of iROS production.
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Int. Immunopharmacol. · Sep 2011
Characterization, epitope identification and mechanisms of the anti-septic capacity of monoclonal antibodies against macrophage migration inhibitory factor.
Sepsis is characterized by uncontrolled inflammatory responses. Macrophage migration inhibitory factor (MIF) has been shown to play an important role in the progression of sepsis thus is a potential therapeutic target. The aim of this study is to produce IgG anti-MIF monoclonal antibodies (mAbs) with anti-septic abilities in vivo and to determine mechanisms of their function. ⋯ Three of the mAbs, F11 in particular, inhibited tautomerase activity in association with their protective effect on CLP mice. Thus, we have produced anti-MIF mAbs that protected mice from CLP-induced sepsis by recognizing the same epitope domains in MIF. These mAbs are promising candidates for further development of therapeutics against inflammatory diseases.