Colon cancer cell-derived high mobility group 1/amphoterin induces growth inhibition and apoptosis in macrophages.
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.
Kuniyasu
Hiroki
H
Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. cooninh@zb4.so-net.ne.jp
Yano
Seiji
S
Sasaki
Takamitsu
T
Sasahira
Tomonori
T
Sone
Sabro
S
Ohmori
Hitoshi
H
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
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
J Cell Sci. 2000 Feb;113 ( Pt 4):611-20
10652254
Biochem Biophys Res Commun. 1999 Aug 27;262(2):350-4
10462478
J Biol Chem. 2000 Sep 1;275(35):26792-8
10854431
FASEB J. 2000 Sep;14(12):1705-14
10973919
Matrix Biol. 2000 Sep;19(5):377-87
10980414
Mol Biol Cell. 2000 Dec;11(12):4347-58
11102528
J Biol Chem. 2000 Dec 22;275(51):40096-105
11007787
Cancer Lett. 2001 Apr 10;165(1):1-10
11248412
J Cell Biol. 2001 Mar 19;152(6):1197-206
11257120
Shock. 2001 Apr;15(4):247-53
11303722
J Biol Chem. 2001 Jul 27;276(30):28113-20
11369774
Mol Med. 2001 May;7(5):293-300
11474575
Mol Cell Biol. 2001 Oct;21(19):6706-17
11533257
Prostate. 2001 Sep 15;49(1):19-29
11550207
Oncogene. 2001 Sep 27;20(43):6263-8
11593437
J Endotoxin Res. 2001;7(4):315-21
11717586
J Pathol. 2002 Feb;196(2):163-70
11793367
Am J Physiol Lung Cell Mol Physiol. 2002 Oct;283(4):L849-58
12225962
Cancer Res. 2002 Dec 1;62(23):7042-9
12460925
Oncol Rep. 2003 Mar-Apr;10(2):445-8
12579287
J Immunol. 2003 Mar 1;170(5):2409-16
12594264
Nat Cell Biol. 2003 Sep;5(9):781-92
12907943
Oncol Rep. 2003 Nov-Dec;10(6):1863-8
14534709
Pathobiology. 2004;71(3):129-36
15051925
Nature. 1979 May 24;279(5711):328-31
450085
J Immunol Methods. 1984 May 25;70(2):257-68
6609997
Annu Rev Med. 1987;38:417-32
3555304
Biochem Biophys Res Commun. 1993 Mar 15;191(2):503-8
7681667
J Biol Chem. 1995 Mar 31;270(13):7394-8
7706284
Nature. 1996 Mar 7;380(6569):75-9
8598911
J Natl Cancer Inst. 1996 Aug 21;88(16):1146-51
8757194
J Immunol. 1996 Sep 15;157(6):2660-5
8805671
Cell Growth Differ. 1997 Jan;8(1):47-52
8993833
J Immunol. 1998 Sep 1;161(5):2490-500
9725248
Oncogene. 1998 Oct 8;17(14):1855-69
9778052
Nature. 2000 May 18;405(6784):354-60
10830965