Ceftiofur impairs pro-inflammatory cytokine secretion through the inhibition of the activation of NF-κB and MAPK
Section snippets
Materials and methods
Reagents. Ceftiofur, dimethyl sulfoxide (DMSO), LPS (Escherichia coli 055:B5), and 3-(4,5-dimethylthiazol-2-y1)-2,5-dipheny-ltetrazolium bromide (MTT) were purchased from Sigma Chemical Co. (St. Louis, MO, USA). Dulbecco’s modified Eagle’s medium (DMEM) and fetal bovine serum (FBS) were obtained from Invitrogen-Gibco (Grand Island, NY). Rabbit anti-NF-κB/p65 polyclonal antibody, rabbit anti-JNK polyclonal antibody, rabbit anti-ERK polyclonal antibody, rabbit anti-p38 polyclonal antibody, mouse
The effect of ceftiofur on macrophage toxicity
Ceftiofur did not display any cellular toxicity against RAW264.7 cells over 24 h, as determined by the MTT assay (Fig. 1).
The effect of ceftiofur on LPS-induced cytokine production in vitro
TNF-α, IL-1β, IL-6, and IL-10 concentrations in the culture supernatants of RAW 264.7 cells were measured by sandwich ELISA (Fig. 2). RAW 264.7 cells treated with LPS produced significant amounts of all cytokines examined. The concentration of TNF-α was up to 18 ng/mL after LPS stimulation. However, the concentration of TNF-α in the supernatant of cells pretreated with 1, 5,
Discussion
When mononuclear phagocytes recognize LPS via cell surface receptors, they release numerous pro-inflammatory cytokines [17]. Excessive production of pro-inflammatory cytokines will result in a systemic inflammatory response syndrome typified by septic shock and the complications that are normally associated with it. It would be desirable to be able to selectively regulate cytokine production in the treatment of inflammatory diseases [18], [19], [20], [21]. Therefore, any intervention that
Acknowledgment
This work was supported by a grant from the National Natural Science Foundation of China (No. 30671586).
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These authors contributed equally to this work.