GYY4137, a hydrogen sulfide‑releasing molecule, inhibits the inflammatory response by suppressing the activation of nuclear factor‑kappa B and mitogen‑activated protein kinases in Coxsackie virus B3‑infected rat cardiomyocytes.
GYY4137 is a water‑soluble, small molecule hydrogen sulfide (H2S)‑release agent that possesses potent cardioprotective and anti‑inflammatory properties in experimental models. Coxsackie virus B3 (CVB3) infection commonly causes viral myocarditis, which mainly involves immune cell infiltration, eventually resulting in heart failure. In the present study, the effects and underlying mechanisms of GYY4137 treatment of CVB3‑induced myocarditis were investigated. The effects of GYY4137 on CVB3‑induced nuclear factor‑kappa B (NF‑κB) activity were examined by western blotting, immunofluorescence and electrophoretic mobility shift assay. Mitogen‑activated protein kinase (MAPK) signaling protein expression levels were detected by western blotting. Cardiomyocyte damage‑related enzyme activities, such as lactate dehydrogenase (LDH) and creatine kinase MB (CK‑MB), were measured by ELISA, as well as the production of proinflammatory cytokines. The results revealed that GYY4137 suppressed CVB3‑induced secretion of LDH, CK‑MB and pro‑inflammatory cytokines, such as tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6. Furthermore, the activation of NF‑κB and the IκBα degradation induced by CVB3 were also inhibited by GYY4137. Notably, the phosphorylation of p38, ERK1/2 and JNK1/2 induced by CVB3 was also inhibited by GYY4137. In conclusion, the data demonstrate that GYY4137 exerts anti‑inflammatory effects in CVB3‑infected cardiomyocytes. This anti‑inflammatory mechanism may be associated with suppression of NF‑κB and MAPK signaling pathway activation.
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Zubo
Z
Wu
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Hua
H
Peng
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Qing
Q
Du
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Wen
W
Lin
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Yali
Y
Liu
D021581:Active Transport, Cell Nucleus; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000150:complications / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D029822:Enterovirus B, Human / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology*; D009205:Myocarditis / Q000188:drug therapy / Q000209:etiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism*; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D021381:Protein Transport; D059748:Proteolysis; D051381:Rats
D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; C529376:GYY 4137; D018836:Inflammation Mediators; D009025:Morpholines; D016328:NF-kappa B; D009946:Organothiophosphorus Compounds; D020928:Mitogen-Activated Protein Kinases; D006862:Hydrogen Sulfide