title: In human macrophages the complement component C5a induces the expression of oncostatin M via AP-1 activation.
abstract: OBJECTIVE
  Macrophages produce the cytokine oncostatin M (OSM), which beside other functions is also involved in inflammation. The complement component C5a mobilizes and activates these cells at inflammatory sites. We examined the effect of C5a on OSM production in human monocytes and in human monocyte-derived macrophages.
  
  
  RESULTS
  For macrophage transformation peripheral blood monocytes were cultivated for 8 to 10 days in the presence of human serum. C5a significantly increased in these cells OSM antigen as determined by specific ELISA and mRNA as quantitated by real-time polymerase chain reaction in these cells as well as in plaque macrophages. This effect was blocked by antibodies against the receptor C5aR/CD88 and by pertussis toxin. The C5a-induced phosphorylation of p38 and JNK and the C5a-induced increase in OSM production in macrophages was abolished by 2 p38 inhibitors and by a JNK inhibitor. Furthermore C5a increased the nuclear translocation of c-fos and c-jun. Using different OSM promoter deletion mutant constructs we show that the putative AP-1 element is responsible for activation of OSM promoter activity by C5a.
  
  
  CONCLUSIONS
  Our data establish a link between the complement system and the gp130 receptor cytokine family with possible implications for the pathology of inflammatory diseases.
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Kastl
authors.forename: Walter S
authors.initials: WS
authors.lastname: Speidl
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Katsaros
authors.forename: Gersina
authors.initials: G
authors.lastname: Rega
authors.forename: Taras
authors.initials: T
authors.lastname: Afonyushkin
authors.forename: Valery N
authors.initials: VN
authors.lastname: Bochkov
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Afshin
authors.initials: A
authors.lastname: Assadian
authors.forename: Georg W
authors.initials: GW
authors.lastname: Hagmueller
authors.forename: Martina
authors.initials: M
authors.lastname: Hoeth
authors.forename: Rainer
authors.initials: R
authors.lastname: de Martin
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Ma
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
mesh_terms: D000704:Analysis of Variance; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D015936:Complement C5a / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*; D011336:Probability; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D053683:Oncostatin M; D015936:Complement C5a