title: Colon cancer cell-derived high mobility group 1/amphoterin induces growth inhibition and apoptosis in macrophages.
abstract: High mobility group (HMGB)1/amphoterin is a multifunctional cytokine involved in invasion and metastasis of cancer and in inflammation. To investigate HMGB1/amphoterin effects on macrophages, U937 human monocytic leukemia cells and rat peritoneal and human alveolar macrophages were examined. U937 cells expressed low levels of an HMGB1/amphoterin receptor, receptor for advanced glycation end-products (RAGE), whereas RAGE production was induced in differentiated phorbol 12-myristate 13-acetate (PMA)-U937 cells. Treatment with cultured medium of HMGB1/amphoterin-secreting WiDr human colon cancer cells showed growth inhibition of both U937 and PMA-U937 cells and apoptosis in PMA-U937 cells. The number of PMA-U937 cells was markedly decreased by co-culture with WiDr cells exposed to HMGB1/amphoterin sense S-oligodeoxynucleotide (ODN) in spheroids or monolayers. In contrast, PMA-U937 cells co-cultured with WiDr cells exposed to HMGB1/amphoterin anti-sense S-ODN were preserved in number. PMA-U937 cells exposed to RAGE anti-sense S-ODN were insensitive to WiDr-cultured medium. Recombinant human HMGB1/amphoterin induced growth inhibition in thioglycollate-induced rat peritoneal macrophages, PMA-U937 cells, and human alveolar macrophages, an effect that was abrogated by absorption with anti-HMGB1 antibody. Phosphorylation of JNK and Rac1 was induced in PMA-U937 cells treated with HMGB1/amphoterin. These results suggest that HMGB1/amphoterin induces growth inhibition and apoptosis in macrophages through RAGE intracellular signaling pathway.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. cooninh@zb4.so-net.ne.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Sabro
authors.initials: S
authors.lastname: Sone
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohmori
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D020298:U937 Cells
chemical_list: D017077:Culture Media, Conditioned; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D009573:Nitrites; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013755:Tetradecanoylphorbol Acetate
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