Ceftiofur impairs pro-inflammatory cytokine secretion through the inhibition of the activation of NF-kappaB and MAPK.
Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use. Immunopharmacological studies can provide new information on the immunomodulatory activities of some drugs, including their effect on cytokine productions. For this reason, we investigated the effect of ceftiofur on cytokine productions in vitro. We found that ceftiofur can downregulate tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), but did not affect interleukin-10 (IL-10) production. We further investigated signal transduction mechanisms to determine how ceftiofur affects. RAW 264.7 cells were pretreated with 1, 5, or 10 mg/L of ceftiofur 1 h prior to treatment with 1 mg/L of LPS. Thirty minutes later, cells were harvested and mitogen activated protein kinases (MAPKs) activation was measured by Western blot. Alternatively, cells were fixed and nuclear factor-kappaB (NF-kappaB) activation was measured using immunocytochemical analysis. Signal transduction studies showed that ceftiofur significantly inhibited extracellular signal-regulated kinase (ERK), p38, and c-jun NH(2)-terminal kinase (JNK) phosphorylation protein expression. Ceftiofur also inhibited p65-NF-kappaB translocation into the nucleus. Therefore, ceftiofur may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kappaB and MAPKs signaling in RAW264.7 cells.
Ci
Xinxin
X
Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China.
Song
Yu
Y
Zeng
Fanqin
F
Zhang
Xuemei
X
Li
Hongyu
H
Wang
Xinrui
X
Cui
Junqing
J
Deng
Xuming
X
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002511:Cephalosporins / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000819:agonists / Q000037:antagonists & inhibitors*
D002511:Cephalosporins; D016207:Cytokines; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; C053503:ceftiofur; D020928:Mitogen-Activated Protein Kinases