The above results suggest that AVP induces IL-6 induction in murine hearts via the V<sub>1A</sub> receptor-mediated β-arrestin2/ERK<sub>1/2</sub>/NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V<sub>1A</sub>/β-arrestin 2/ERK<sub>1/2</sub>/NF-κB signaling pathway.
Our data revealed that (1) the P-AKT2/SPK1 (P-SPK1) and P-MEK/P-ERK signaling cascades acted separately in the regulation of macrophage migration; (2) P-AKT2/SPK1 (P-SPK1) played a relatively important role compared to P-MEK/P-ERK cell signaling in LPS-induced macrophage migration; (3) atorvastatin (ATV) inhibited macrophage migration by inhibiting P-AKT2/SPK1 (P-SPK1) cell signaling, but ATV could increase P-MEK and P-ERK protein expression; (4) ATV has a beneficial effect on LPS-induced myocarditis via inhibition of P-AKT2/SPK1-mediated macrophage recruitment, apoptosis, TNFα, IL-1β, and IL-6; (5) ATV-offered protection against LPS-induced myocarditis was eliminated from SPK1-KO mice; (6) SPK1 may play a harmful role in LPS-induced myocarditis.
On the other hand, STAT3 contributes to immune-mediated myocarditis due to IL-6-induced complement component C3 production in the liver, as well as the differentiation of Th17 cells, which play a role in initiation and development of myocarditis.
We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral myocarditis.
While experimental models of myocarditis have clearly linked IL-6 to the generation of pathogenic autoreactive T cells, IL-6 has exhibited a protective role in autoimmune disease development in viral-induced disease models.
Using reverse transcriptase polymerase chain reaction (RT-PCR), we examined the expression of interleukin 1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha) and the presence of enteroviral genomic RNA in endomyocardial biopsy tissues obtained from patients with myocarditis and DCM.