Cytokine signaling during myocardial infarction: sequential appearance of IL-1 beta and IL-6

Guillén, Ivalena; Blanes, Margarita; Gómez‐Lechón, M. José; Castell, J. V.

doi:10.1152/ajpregu.1995.269.2.r229

Cited by 122 publications

(107 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Marked IL-1 upregulation has been reported in experimental models of myocardial infarction [142], [11]. In addition, a significant increase in IL-1β plasma levels has been documented in patients with acute myocardial infarction [159]. However, despite extensive descriptive evidence suggesting involvement of IL-1 in infarct healing, information regarding its biological role in myocardial infarction is limited.…”

Section: The Il-1 Familymentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

572

499

View full text Add to dashboard Cite

Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

show abstract

Section: The Il-1 Familymentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

572

499

View full text Add to dashboard Cite

show abstract

“…After binding to its receptor, IL-6 elicits numerous effects including antibody induction, hematopoiesis, thrombocytopoiesis, and acute-phase protein synthesis (1,2). Significant increases in serum levels of IL-6 and its mRNA and protein expression in cardiac tissues have been reported in patients with several cardiac diseases including congestive heart failure (3-5), myocarditis (3), septic cardiomyopathy (6), myocardial infarction (7)(8)(9), cardiac myxoma (10), and the cell injury associated with ischemia/reperfusion (11) and cardiopulmonary bypass (12). Thus, IL-6 has been suggested to play an important role in the pathophysiology of these cardiac disorders.…”

Section: Il-6mentioning

confidence: 99%

JAK2/STAT3, Not ERK1/2, Mediates Interleukin-6-induced Activation of Inducible Nitric-oxide Synthase and Decrease in Contractility of Adult Ventricular Myocytes

Kennedy

Liu

2003

Journal of Biological Chemistry

135

119

View full text Add to dashboard Cite

Interleukin (IL)-6 decreases cardiac contractility via a nitric oxide (NO)-dependent pathway. However, mechanisms underlying IL-6-induced NO production remain unclear. JAK2/STAT3 and ERK1/2 are two well known signaling pathways activated by IL-6 in non-cardiac cells. However, these IL-6-activated pathways have not been identified in adult cardiac myocytes. In this study, we identified activation of these two pathways during IL-6 stimulation and examined their roles in IL-6-induced NO production and decrease in contractility of adult ventricular myocytes. IL-6 increased phosphorylation of STAT3 (at Tyr 705 ) and ERK1/2 (at Tyr 204 ) within 5 min that peaked at 15-30 min and returned to basal levels at 2 h. Phosphorylation of STAT3 was blocked by genistein, a protein tyrosine kinase inhibitor, and AG490, a JAK2 inhibitor, but not PD98059, an ERK1/2 kinase inhibitor. The phosphorylation of ERK1/2 was blocked by PD98059 and genistein but not AG490. Furthermore, IL-6 enhanced de novo synthesis of iNOS protein, increased NO production, and decreased cardiac contractility after 2 h of incubation. These effects were blocked by genistein and AG490 but not PD98059. We conclude that IL-6 activated independently the JAK2/STAT3 and ERK1/2 pathways, but only JAK2/ STAT3 signaling mediated the NO-associated decrease in contractility.

show abstract

“…Coincidentally, a marked upregulation of IL-1 has been found in ischemic hearts. [12][13][14] Therefore, understanding the mechanism of IL-1β-mediated cardiomyocyte apoptosis is important in the designing of optimal therapeutic approaches to counter heart failure. In the current study, we used cardiomyocytes isolated from neonatal mice and explored the molecular pathways involved in IL-1β-mediated cardiomyocyte apoptosis in vitro, including caspase-dependent pathways, caspase-independent pathways, and inhibitor of apoptosis proteins (IAPs).…”

mentioning

confidence: 99%