HDL/apolipoprotein A-I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins

Hanayuki Okura, Shizuya Yamashita, Tohru Ohama, Ayami Saga, Aya Yamamoto-Kakuta, Yoko Hamada, Nagako Sougawa, Reiko Ohyama, Yoshiki Sawa, Akifumi Matsuyama

Research output: Contribution to journalArticle

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Abstract

Aim: HDL has anti-inflammatory effects on macrophages, although the mechanism of action remains unclear. We hypothesized that HDL suppresses the conversion of macrophage-secreted factors into proinflammatory factors via binding, and tried to identify the factor that could form a complex with HDL and/or apolipoprotein (apo) A-I. Methods and Results: In conditioned media obtained from human monocyte-derived macrophages, we found an apo A-I binding protein and identified the protein as progranulin/proepithelin/acrogranin/PCDGF. Co-immunoprecipitation analysis showing that progranulin binds and forms a complex with apo A-I and the presence of progranulin in the HDL fraction in the sera indicated that progranilin is a novel apolipoprotein. Conditioned media of HEK293 cells transfected with progranulin augmented the expression of TNF-alpha and IL-1-beta on macrophages, but these effects of progranulin were inhibited by co-incubation with HDL or apo A-I. Anti-progranulin antibodies also reduced the expression of TNF-alpha and IL-1-beta on macrophages. Granulins as conversion products derived from progranilin increased TNF-alpha and IL-1-beta expression and the effects were not suppressed by HDL. Conclusions: Our results suggest that the anti-inflammatory effects of HDL on macrophages might be due to suppression of the conversion of progranulin into proinflammatory granulins by forming a complex.

Original languageEnglish
Pages (from-to)568-577
Number of pages10
JournalJournal of Atherosclerosis and Thrombosis
Volume17
Issue number6
DOIs
Publication statusPublished - 01-01-2010

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Macrophages
Apolipoprotein A-I
Interleukin-1beta
Tumor Necrosis Factor-alpha
Conditioned Culture Medium
Anti-Inflammatory Agents
Apolipoproteins
HEK293 Cells
Immunoprecipitation
granulin precursor protein
Anti-Idiotypic Antibodies
Carrier Proteins
Antibodies
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

Cite this

Okura, Hanayuki ; Yamashita, Shizuya ; Ohama, Tohru ; Saga, Ayami ; Yamamoto-Kakuta, Aya ; Hamada, Yoko ; Sougawa, Nagako ; Ohyama, Reiko ; Sawa, Yoshiki ; Matsuyama, Akifumi. / HDL/apolipoprotein A-I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins. In: Journal of Atherosclerosis and Thrombosis. 2010 ; Vol. 17, No. 6. pp. 568-577.
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HDL/apolipoprotein A-I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins. / Okura, Hanayuki; Yamashita, Shizuya; Ohama, Tohru; Saga, Ayami; Yamamoto-Kakuta, Aya; Hamada, Yoko; Sougawa, Nagako; Ohyama, Reiko; Sawa, Yoshiki; Matsuyama, Akifumi.

In: Journal of Atherosclerosis and Thrombosis, Vol. 17, No. 6, 01.01.2010, p. 568-577.

Research output: Contribution to journalArticle

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T1 - HDL/apolipoprotein A-I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins

AU - Okura, Hanayuki

AU - Yamashita, Shizuya

AU - Ohama, Tohru

AU - Saga, Ayami

AU - Yamamoto-Kakuta, Aya

AU - Hamada, Yoko

AU - Sougawa, Nagako

AU - Ohyama, Reiko

AU - Sawa, Yoshiki

AU - Matsuyama, Akifumi

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N2 - Aim: HDL has anti-inflammatory effects on macrophages, although the mechanism of action remains unclear. We hypothesized that HDL suppresses the conversion of macrophage-secreted factors into proinflammatory factors via binding, and tried to identify the factor that could form a complex with HDL and/or apolipoprotein (apo) A-I. Methods and Results: In conditioned media obtained from human monocyte-derived macrophages, we found an apo A-I binding protein and identified the protein as progranulin/proepithelin/acrogranin/PCDGF. Co-immunoprecipitation analysis showing that progranulin binds and forms a complex with apo A-I and the presence of progranulin in the HDL fraction in the sera indicated that progranilin is a novel apolipoprotein. Conditioned media of HEK293 cells transfected with progranulin augmented the expression of TNF-alpha and IL-1-beta on macrophages, but these effects of progranulin were inhibited by co-incubation with HDL or apo A-I. Anti-progranulin antibodies also reduced the expression of TNF-alpha and IL-1-beta on macrophages. Granulins as conversion products derived from progranilin increased TNF-alpha and IL-1-beta expression and the effects were not suppressed by HDL. Conclusions: Our results suggest that the anti-inflammatory effects of HDL on macrophages might be due to suppression of the conversion of progranulin into proinflammatory granulins by forming a complex.

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