title: Role of cell-cell interactions in high mobility group box 1 cytokine activity in human peripheral blood mononuclear cells and mouse splenocytes.
abstract: Cell-cell interaction through binding of intercellular adhesion molecule (ICAM), B7.1, B7.2 and CD40 on monocytes to their ligands on T-cells plays a number of roles in cytokine . High mobility group box 1 (HMGB1), an abundant and conserved nuclproduction and lymphocyte proliferationear protein, acts in the extracellular environment as a primary pro-inflammatory signal. The receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)-2 and TLR-4 are receptors for HMGB1. HMGB1 induces pro-inflammatory cytokine production in monocytes and T-cells. This study was designed to study the cellular mechanism of cytokine production. HMGB1 concentration-dependently induced ICAM-1, B7.1, B7.2 and CD40 expression on monocytes, and interferon (IFN)-γ and tumor necrosis factor (TNF)-α production and lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs). These HMGB1 activities depended on the stimulation of RAGE on monocytes. HMGB1 also up-regulated RAGE, but not TLR-2 or TLR-4, expression on monocytes, which was inhibited by antibodies (Abs) against ICAM-1, B7.1, B7.2 and CD40. These results together indicated that HMGB1 could induce an intimate cellular interplay between monocytes and T-cells in PBMCs through the stimulation and up-regulation of RAGE and other adhesive molecules on monocytes.
authors.affiliation: Department of Pharmacology, Kinki University, Osaka-Sayama, Osaka, Japan. hkt@med.kindai.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Kohka Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.forename: Hidenori
authors.initials: H
authors.lastname: Wake
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma