β-arrestin2 in Infiltrated Macrophages Inhibits Excessive Inflammation after Myocardial Infarction

Kenji Watari, Nakaya Michio, Motohiro Nishida, Kyeong Man Kim, Hitoshi Kurose

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Beta-arrestins (β-arrestin1 and β-arrestin2) are known as cytosolic proteins that mediate desensitization and internalization of activated G protein-coupled receptors. In addition to these functions, β-arrestins have been found to work as adaptor proteins for intracellular signaling pathways. β-arrestin1 and β-arrestin2 are expressed in the heart and are reported to participate in normal cardiac function. However, the physiological and pathological roles of β-arrestin1/2 in myocardial infarction (MI) have not been examined. Here, we demonstrate that β-arrestin2 negatively regulates inflammatory responses of macrophages recruited to the infarct area. β-arrestin2 knockout (KO) mice have higher mortality than wild-type (WT) mice after MI. In infarcted hearts, β-arrestin2 was strongly expressed in infiltrated macrophages. The production of inflammatory cytokines was enhanced in β-arrestin2 KO mice. In addition, p65 phosphorylation in the macrophages from the infarcted hearts of β-arrestin2 KO mice was increased in comparison to that of WT mice. These results suggest that the infiltrated macrophages of β-arrestin2 KO mice induce excessive inflammation at the infarct area. Furthermore, the inflammation in WT mice transplanted with bone marrow cells of β-arrestin2 KO mice is enhanced by MI, which is similar to that in β-arrestin2 KO mice. In contrast, the inflammation after MI in β-arrestin2 KO mice transplanted with bone marrow cells of WT mice is comparable to that in WT mice transplanted with bone marrow cells of WT mice. In summary, our present study demonstrates that β-arrestin2 of infiltrated macrophages negatively regulates inflammation in infarcted hearts, thereby enhancing inflammation when the β-arrestin2 gene is knocked out. β-arrestin2 plays a protective role in MI-induced inflammation.

Original languageEnglish
Article numbere68351
JournalPloS one
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 8 2013

Fingerprint

Macrophages
myocardial infarction
Knockout Mice
macrophages
inflammation
Myocardial Infarction
Inflammation
Arrestins
mice
Bone
Cells
Bone Marrow Cells
Intracellular Signaling Peptides and Proteins
bone marrow cells
Phosphorylation
heart
arrestins
G-Protein-Coupled Receptors
infarction
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

β-arrestin2 in Infiltrated Macrophages Inhibits Excessive Inflammation after Myocardial Infarction. / Watari, Kenji; Michio, Nakaya; Nishida, Motohiro; Kim, Kyeong Man; Kurose, Hitoshi.

In: PloS one, Vol. 8, No. 7, e68351, 08.07.2013.

Research output: Contribution to journalArticle

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