Immunological Behavior Analysis of Muscle Cells under IFN‐γ Stimulation in Vitro and in Vivo

Abstract

Muscle cells could serve as antigen-presenting cells, and participate in the activation of immune response. Immunological characteristics of muscle cells, and their capacities to equip themselves with immunorelevant molecules, remain to be elucidated. In this study, we investigated the immunological properties of myoblasts and differentiated myotubes in vitro and in vivo, under the IFN-γ induced inflammatory condition. We found that the fused C C myotubes are more sensitive to inflammatory stimulation, and significantly upregulated the expression levels of MHC-I/II and TLR3/7 molecules, than that of proliferated myoblasts. As well, some co-stimulatory/-inhibitory molecules, including CD40, CD86, ICAM-I, ICOS-L, and PD-L1, were prominently upregulated in IFN-γ induced myotubes. Notably, we detected the protein levels of ASC, NLRP3, and Caspase-1 increased in stimulated myotubes, and IL-1β in cell culture supernatant, implying the activation of NLRP3 inflammasomes in IFN-γ treated myotubes. The pro-inflammatory cytokines and chemokines mRNA levels in IFN-γ induced C C myotubes and myoblasts, involving IL-1, IL-6, and MCP-1, increased markedly. T cell activation test further verified IFN-γ induced C C myotubes prompt to the proliferation of the splenic CD4 and CD8 T cells. In Cardiotoxin-damaged tibialis anterior (TA) muscle, some regenerated myofibers expressed both MHC class I and class II molecules under IFN-γ enhanced inflammatory condition. Thus, our work demonstrates that muscle cells are active participants of local immune reactions. Anat Rec, 301:1551-1563, 2018. © 2018 Wiley Periodicals, Inc.

Low-dose Diosbulbin-B (DB) Regulates Tumor-Intrinsic PD-L1/NLRP3 Signaling Pathway to Increase Cisplatin-Sensitivity in Gastric Cancer (GC)

“…Consistently, knock-down of NLRP3 abrogated the promoting effects of cisplatin-DB combined treatment on cell apoptosis in CR-GC cells, which were in accordance with the previous studies [38,40,41]. Furthermore, the intrinsic PD-L1/NLRP3 pathway had been reported in the previous studies [31] [32], and we validated that low-dose DB inhibited PD-L1 expressions to activate NLRP3 mediated cell pyroptosis in cisplatin treated CR-GC cells.…”

“…For example, myeloid phosphate and tension homology deleted on chromosome ten (PTEN) promoted chemotherapy-induced NLRP3 mediated cell pyroptosis to inhibit cancer development [30], and activation of NLRP3-mediated pyroptotic cell death enhanced the cytotoxic effects of cisplatin in non-small cell lung cancer (NSCLC) [29]. Of note, Bala et al validated that there existed an intrinsic PD-L1/NLRP3 signaling pathway in melanoma cells [31], and the correlations between PD-L1 and NLRP3 had also been observed in interferon-γ (IFN-γ) induced myotubes [32]. However, the detailed information for the PD-L1-NLRP3 pathway had not been deeply investigated in other types of cells, such as GC cells.…”

Involvement of inflammasome activation via elevation of uric acid level in nociception in a mouse model of muscle pain

“…There are a few reports of NLRP3 inflammasome activation in skeletal muscle cell. 47,48 Ding et al. reported NLRP3 inflammasome activation in interferon gamma (IFN-γ) treated C2C12 cultured myotubes.…”

“…reported NLRP3 inflammasome activation in interferon gamma (IFN-γ) treated C2C12 cultured myotubes. 47 McBride et al. reported that NLRP3 inflammasome contributes to sarcopenia.…”

Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells

“…Myoblasts and myotubes can express a surprising variety of immunologically important molecules, including class I/II major histocompatibility complex (MHC-I/II) and co-stimulatory molecules in the presence of IFN-γ or other proinflammatory cytokines [47, 48]; this suggests that, under proinflammatory environment, muscle cells can actively participate in local immune reactions. We have demonstrated that estrogen signaling contributed to muscle inflammation response, which could reflect that estrogen signaling possibly affects on intrinsic immunological capacities of muscle cells, like it does for immune cells.…”