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In the present report, however, we demonstrate antiproliferative activity of recombinant human (rh) granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) on mono\u2010blast cell line U\u2010937 and provide evidence for the involvement of tumor necrosis factor alpha TNF\u2010\u03b1 and interleukin 1 beta (IL 1\u03b2) in its growth inhibitory action. GM\u2010CSF (but not granulocyte CSF, G\u2010CSF or macrophage CSF, M\u2010CSF) suppressed DNA synthesis and self renewal of U\u2010937 cells. Similarly, medium conditioned by U\u2010937 cells in response to GM\u2010CSF (GM\u2010CSF U\u2010937\u2010CM) was able to reduce clonogenicity and [<jats:sup>3<\/jats:sup>H] thymidine uptake by U\u2010937 cells. Since neutralization of GM\u2010CSF present in GM\u2010CSF U\u2010937\u2010CM by monoclonal antibody to GM\u2010CSF did not abrogate the autoinhibitory activity present in GM\u2010CSF U\u2010937\u2010CM, we considered the possibility that other soluble molecules are released by U\u2010937 cells upon GM\u2010CSF stimulation. Neutralization by antibodies to IL1\u03b2 and TNF\u2010\u03b1 suggested that both monokines could be the antiproliferative principle operating in GM\u2010CSF U\u2010937\u2010CM. Moreover, employing IL 1\u03b2\u2010specific enzyme\u2010linked immunosorbent assay, TNF\u2010\u03b1 specific radioimmunoassay, Northern analysis using a cloned TNF\u2010\u03b1\u2010specific cDNA and an oligonucleotide probe for IL 1\u03b2, we demonstrate GM\u2010CSF\u2010inducible IL 1\u03b2 and TNF\u2010\u03b1 gene expression by U\u2010937 cells at the mRNA and protein level. Although M\u2010CSF expression was induced under similar conditions, M\u2010CSF failed to inhibit growth of U\u2010937 cells.<\/jats:p>","DOI":"10.1002\/eji.1830180308","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T01:15:11Z","timestamp":1172711711000},"page":"369-374","source":"Crossref","is-referenced-by-count":30,"title":["Recombinant human granulocyte\u2010macrophage colony\u2010stimulating factor induces secretion of autoinhibitory monokines by U\u2010937 cells"],"prefix":"10.1002","volume":"18","author":[{"given":"Albrecht","family":"Lindemann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlev","family":"Riedel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfang","family":"Oster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Mertelsmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedhelm","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,22]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.4049\/jimmunol.136.11.4106","volume":"136","author":"Meuer S. 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