PMID- 18474228 OWN - NLM STAT- MEDLINE DCOM- 20080620 LR - 20141120 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 372 IP - 1 DP - 2008 Jul 18 TI - Ceftiofur impairs pro-inflammatory cytokine secretion through the inhibition of the activation of NF-kappaB and MAPK. PG - 73-7 LID - 10.1016/j.bbrc.2008.04.170 [doi] AB - 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. FAU - Ci, Xinxin AU - Ci X AD - Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China. FAU - Song, Yu AU - Song Y FAU - Zeng, Fanqin AU - Zeng F FAU - Zhang, Xuemei AU - Zhang X FAU - Li, Hongyu AU - Li H FAU - Wang, Xinrui AU - Wang X FAU - Cui, Junqing AU - Cui J FAU - Deng, Xuming AU - Deng X LA - eng PT - Journal Article DEP - 20080512 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Cephalosporins) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Transcription Factor RelA) RN - 83JL932I1C (ceftiofur) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Active Transport, Cell Nucleus/drug effects MH - Animals MH - Cell Line MH - Cell Nucleus/metabolism MH - Cephalosporins/*pharmacology MH - Cytokines/*metabolism MH - Lipopolysaccharides/immunology/pharmacology MH - Macrophages/*drug effects/immunology MH - Mice MH - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism MH - Signal Transduction/drug effects MH - Transcription Factor RelA/agonists/*antagonists & inhibitors EDAT- 2008/05/14 09:00 MHDA- 2008/06/21 09:00 CRDT- 2008/05/14 09:00 PHST- 2008/04/22 00:00 [received] PHST- 2008/04/28 00:00 [accepted] PHST- 2008/05/14 09:00 [pubmed] PHST- 2008/06/21 09:00 [medline] PHST- 2008/05/14 09:00 [entrez] AID - S0006-291X(08)00859-0 [pii] AID - 10.1016/j.bbrc.2008.04.170 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2008 Jul 18;372(1):73-7. doi: 10.1016/j.bbrc.2008.04.170. Epub 2008 May 12.