title: The Protective Role of Interleukin-33 in Myocardial Ischemia and Reperfusion Is Associated with Decreased HMGB1 Expression and Up-Regulation of the P38 MAPK Signaling Pathway.
abstract: Interleukin-33 (IL-33) plays a protective role in myocardial ischemia and reperfusion (I/R) injury, but the underlying mechanism was not fully elucidated. The present study was designed to investigate whether IL-33 protects against myocardial I/R injury by regulating both P38 mitogen-activated-protein kinase (P38 MAPK), which is involved in one of the downstream signaling pathways of IL-33, and high mobility group box protein 1 (HMGB1), a late pro-inflammatory cytokine. Myocardial I/R injury increased the level of IL-33 and its induced receptor (sST) in myocardial tissue. Compared with the I/R group, the IL-33 group had significantly lower cardiac injury (lower serum creatine kinase (CK), lactate dehydrogenase (LDH), and cTnI levels and myocardial infarct size), a suppressed inflammatory response in myocardial tissue (lower expression of HMGB1, IL-6, TNF-α and INF-γ) and less myocardial apoptosis (much higher Bcl-2/Bax ratio and lower cleaved caspase-3 expression). Moreover, IL-33 activated the P38 MAPK signaling pathway (up-regulating P-P38 expression) in myocardial tissue, and SB230580 partially attenuated the anti-inflammatory and anti-apoptosis effects of IL-33. These findings indicated that IL-33 protects against myocardial I/R injury by inhibiting inflammatory responses and myocardial apoptosis, which may be associated with the HMGB1 and P38 MAPK signaling pathways.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Ma
authors.initials: M
authors.lastname: Ruisong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Xiaorong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Gangying
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chunfeng
authors.affiliation: Department of Cardiology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Changjiang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xuefei
authors.affiliation: Department of Cardiology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuanhong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008297:Male; D017202:Myocardial Ischemia / Q000276:immunology*; D032383:Myocytes, Cardiac; D065840:Protective Factors; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; C553108:Il33 protein, rat; D000067596:Interleukin-33