{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:39:40Z","timestamp":1790987980235,"version":"4.1.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,3,1]]},"abstract":"<jats:p>Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine that has an important role in the pathogenesis of inflammation, cachexia, and septic shock. Although TNF-alpha is mainly produced by macrophages, there is evidence regarding TNF-alpha production by cells that are not derived from bone marrow. TNF-alpha production by normal and inflamed human liver was assessed at both mRNA and protein levels. Using a wide panel of novel anti-TNF-alpha monoclonal antibodies and a specific polyclonal antiserum, TNF-alpha immunoreactivity was found in hepatocytes from patients chronically infected with either hepatitis B virus (HBV) or hepatitis C virus. Minimal TNF-alpha immunoreactivity was detected in the mononuclear cell infiltrate and Kupffer cells. In situ hybridization experiments using a TNF-alpha RNA probe showed a significant expression of TNF-alpha mRNA in hepatocytes, Kupffer cells, and some infiltrating mononuclear cells. By contrast, TNF-alpha was detected at low levels in liver biopsies from normal individuals or patients with alcoholic liver disease and low expression of TNF-alpha mRNA was observed in these specimens. Transfection of HepG2 hepatoblastoma cells with either HBV genome or HBV X gene resulted in induction of TNF-alpha expression. Our results demonstrate that viral infection induces, both in vivo and in vitro, TNF-alpha production in hepatocytes, and indicate that the HBV X protein may regulate the expression of this cytokine. These findings suggest that TNF-alpha may have an important role in human liver diseases induced by viruses.<\/jats:p>","DOI":"10.1084\/jem.179.3.841","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"841-848","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":213,"title":["Induction of tumor necrosis factor alpha production by human hepatocytes in chronic viral hepatitis."],"prefix":"10.1084","volume":"179","author":[{"given":"R","family":"Gonz\u00e1lez-Amaro","sequence":"first","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Garc\u00eda-Monz\u00f3n","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Garc\u00eda-Buey","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Moreno-Otero","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"Alonso","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Yag\u00fce","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P","family":"Pivel","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"L\u00f3pez-Cabrera","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Fern\u00e1ndez-Ruiz","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"S\u00e1nchez-Madrid","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Inmunolog\u00eda, Hospital de la Princesa, Universidad Aut\u00f3noma de Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1994,3,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/3\/841\/1675516\/841.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/3\/841\/1675516\/841.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T05:54:01Z","timestamp":1690264441000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/179\/3\/841\/50301\/Induction-of-tumor-necrosis-factor-alpha"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1994,3,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.179.3.841","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,3,1]]}}}