In human macrophages the complement component C5a induces the expression of oncostatin M via AP-1 activation.
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.
Kastl
Stefan P
SP
Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Speidl
Walter S
WS
Kaun
Christoph
C
Katsaros
Katharina M
KM
Rega
Gersina
G
Afonyushkin
Taras
T
Bochkov
Valery N
VN
Valent
Peter
P
Assadian
Afshin
A
Hagmueller
Georg W
GW
Hoeth
Martina
M
de Martin
Rainer
R
Ma
Yongsheng
Y
Maurer
Gerald
G
Huber
Kurt
K
Wojta
Johann
J
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
D018836:Inflammation Mediators; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D053683:Oncostatin M; D015936:Complement C5a