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The numbers of necrotic and apoptotic hepatocytes in the liver, as well as the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT), were increased significantly by GalN\/LPS treatment compared to the appropriate controls. Pretreatment with histamine ameliorated the GalN\/LPS\u2010induced necrotic and apoptotic changes in the hepatocytes and inhibited the elevation of serum AST and ALT levels. Histamine attenuated the GalN\/LPS\u2010induced increases in the levels of TNF\u2010\u03b1, but augmented those of IL\u201010 both in the liver and serum. Histamine inhibited the GalN\/LPS\u2010induced caspase\u20103 activity in the liver. Furthermore, these effects of histamine were completely or partially attenuated in H\n                    <jats:sub>2<\/jats:sub>\n                    \u2010R KO mice, but not in H\n                    <jats:sub>1<\/jats:sub>\n                    \u2010R KO mice. Peritoneal macrophages from H\n                    <jats:sub>2<\/jats:sub>\n                    \u2010R KO mice exhibited blunted changes in the effects of histamine on LPS\u2010induced TNF\u2010\u03b1 and IL\u201010 production in vitro compared to the wild\u2010type (WT) controls. In summary, the present findings suggest that the histamine H\n                    <jats:sub>2<\/jats:sub>\n                    \u2010R\u2010TNF\u2010\u03b1 and \u2010IL\u201010 pathways play protective roles in endotoxin\u2010induced hepatic injury. Masaki, T., Chiba, S., Tatsukawa, H., Noguchi, H., Kakuma, T., Endo, M., Seike, M., Watanabe, T., Yoshimatsu, H. The role of histamine H\n                    <jats:sub>1<\/jats:sub>\n                    receptor and H\n                    <jats:sub>2<\/jats:sub>\n                    receptor in LPS\u2010induced liver injury. FASEB J. 19, 1245\u20131252 (2005)\n                  <\/jats:p>","DOI":"10.1096\/fj.04-3195com","type":"journal-article","created":{"date-parts":[[2005,7,28]],"date-time":"2005-07-28T19:23:04Z","timestamp":1122578584000},"page":"1245-1252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The role of histamine H\n                    <sub>1<\/sub>\n                    receptor and H\n                    <sub>2<\/sub>\n                    receptor in LPS\u2010induced liver injury"],"prefix":"10.1096","volume":"19","author":[{"given":"Takayuki","family":"Masaki","sequence":"first","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]},{"given":"Seiichi","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]},{"given":"Hiroshi","family":"Tatsukawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]},{"given":"Hitoshi","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]},{"given":"Tetsuya","family":"Kakuma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]},{"given":"Mizuki","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]},{"given":"Masataka","family":"Seike","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]},{"given":"Takeshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory for Immune Surveillance RIKEN Research Center for Allergy and Immunology  Yokohama Japan"}]},{"given":"Hironobu","family":"Yoshimatsu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Oita University  Oita Japan"}]}],"member":"311","published-online":{"date-parts":[[2005,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007247"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2000.02074.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/09680519020080050501"},{"key":"e_1_2_6_5_1","first-page":"521","article-title":"The role of macrophages in LPS\u2010induced lethality and tissue injury","volume":"63","author":"Groeneveld P. 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