Beta 2-microglobulin modified with advanced glycation end products induces interleukin-6 from human macrophages: role in the pathogenesis of hemodialysis-associated amyloidosis.
Recently, we demonstrated that beta 2-microglobulin (beta 2M) of amyloid deposits in hemodialysis-associated amyloidosis (HAA), a serious complication leading to hemodialysis arthropathy, is modified with advanced glycation end products (AGEs) of the Maillard reaction. In the present study, to elucidate the possible involvement of AGEs-modified beta 2M (AGE-beta 2M) in the pathogenesis of HAA, we examined the effect of AGE-beta 2M on macrophage production of interleukin-6 (IL-6), an important cytokine for osteoclastogenesis and bone resorption. Purified AGE-beta 2M from long-term hemodialysis patients, but not normal beta 2M, stimulated synthesis and secretion of IL-6 from macrophages. Similar effects were also induced by in vitro-prepared AGE-beta 2M (normal beta 2M incubated with glucose for 60 days in vitro). These findings suggested a potential role of AGE-beta 2M in the pathogenesis of HAA.
Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
Y
Y
Iida
T
T
Miyata
R
R
Inagi
S
S
Sugiyama
K
K
Maeda
D000686:Amyloidosis / Q000209:etiology*; D001483:Base Sequence; D001862:Bone Resorption; D017931:DNA Primers / Q000737:chemistry; D017127:Glycation End Products, Advanced; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D006435:Renal Dialysis / Q000009:adverse effects*; D013329:Structure-Activity Relationship; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000494:pharmacology*
D017931:DNA Primers; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D001613:beta 2-Microglobulin