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. METHODS AND 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.
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. METHODS AND 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: Griet A Van Roey; Christopher C Vanison; Jeffanie Wu; Julia H Huang; Lydia A Suh; Roderick G Carter; James E Norton; Stephanie Shintani-Smith; David B Conley; Kevin C Welch; Anju T Peters; Leslie C Grammer; Kathleen E Harris; Kathryn E Hulse; Atsushi Kato; Whitney W Stevens; Robert C Kern; Robert P Schleimer; Bruce K Tan Journal: J Allergy Clin Immunol Date: 2016-12-12 Impact factor: 10.793
Authors: Kathryn L Pothoven; James E Norton; Lydia A Suh; Roderick G Carter; Kathleen E Harris; Assel Biyasheva; Kevin Welch; Stephanie Shintani-Smith; David B Conley; Mark C Liu; Atsushi Kato; Pedro C Avila; Qutayba Hamid; Leslie C Grammer; Anju T Peters; Robert C Kern; Bruce K Tan; Robert P Schleimer Journal: J Allergy Clin Immunol Date: 2016-12-18 Impact factor: 10.793
Authors: Maren Luchtefeld; Christoph Preuss; Frank Rühle; Eskindir P Bogalle; Anika Sietmann; Stefanie Figura; Werner Müller; Karsten Grote; Bernhard Schieffer; Monika Stoll Journal: PLoS One Date: 2011-05-04 Impact factor: 3.240
Authors: Krzysztof Kiryluk; Yifu Li; Simone Sanna-Cherchi; Mersedeh Rohanizadegan; Hitoshi Suzuki; Frank Eitner; Holly J Snyder; Murim Choi; Ping Hou; Francesco Scolari; Claudia Izzi; Maddalena Gigante; Loreto Gesualdo; Silvana Savoldi; Antonio Amoroso; Daniele Cusi; Pasquale Zamboli; Bruce A Julian; Jan Novak; Robert J Wyatt; Krzysztof Mucha; Markus Perola; Kati Kristiansson; Alexander Viktorin; Patrik K Magnusson; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Kari Stefansson; Anne Boland; Marie Metzger; Lise Thibaudin; Christoph Wanner; Kitty J Jager; Shin Goto; Dita Maixnerova; Hussein H Karnib; Judit Nagy; Ulf Panzer; Jingyuan Xie; Nan Chen; Vladimir Tesar; Ichiei Narita; Francois Berthoux; Jürgen Floege; Benedicte Stengel; Hong Zhang; Richard P Lifton; Ali G Gharavi Journal: PLoS Genet Date: 2012-06-21 Impact factor: 5.917