A role for c-Myc in regulating anti-mycobacterial responses

Abstract

c-Myc (Myc) is a well known transcription factor that regulates many essential cellular processes; however, its role in modulating immunity is not known. Here, we showed different species of mycobacteria can induce Myc expression via ERK1/2 and JNK activation. Unexpectedly, the induced Myc is localized in the cytoplasm but not in the nucleus. This induced Myc expression is associated with the induction of TNF-α and IL-6 and with the suppression of intracellular mycobacterial growth. To delineate the underlying mechanisms, we demonstrated that Myc enhances IRAK1 degradation, leading to specific activations of ERK1/2 and p38 MAPK but not Akt, and reduces IκBα protein recovery upon degradation. Hence, our findings may provide insights into a potential role for Myc in regulating the antimicrobial responses.cytokine | macrophages

A role for interleukin‐17A in modulating intracellular survival of Mycobacterium bovis bacillus Calmette–Guérin in murine macrophages

“…38 000 molecular weight glycolipoprotein) of mycobacteria to Toll‐like receptor 2 triggers the activation of multiple MAPKs in macrophages . Consistent with our previous studies, our results demonstrated that BCG is able to induce the phosphorylation of JNK, ERK1/2 and p38 MAPK and also translocation of NF‐κB p65 in macrophages. Our results revealed that IL‐17A specifically enhanced BCG‐induced phosphorylation of JNK in macrophages.…”

“…Signalling pathways of MAPK, including JNK, ERK1/2 and p38 MAPK, are activated in macrophages in response to mycobacterial infection, leading to production of pro‐inflammatory cytokines . The expression of iNOS has also been shown to be regulated by those MAPK pathways .…”

“…After 2 hr (phagocytosis assay) or 48 hr (bacteria survival assay) of BCG infection, the intracellular bacteria were recovered based on the methods described previously. 21 Briefly, the infected macrophages were washed thrice with PBS. The cells were then lysed by lysis buffer (PBS, 0Á5% Triton X-100) to recover intracellular bacteria.…”

Intratracheal administration of p38α short-hairpin RNA plasmid ameliorates lung ischemia-reperfusion injury in rats

“…c-Myc is a well known downstream target of p38␣ and is known to be important in inflammation and apoptosis. 28,29 In the present study, p38␣ and downstream (c-Myc) signals were both inhibited, confirming that the intratracheal administration of pcDNATM6.2-GW/EmGFP-miR expressing the p38MAPK␣ shRNA vector effectively silenced the p38␣ gene pathway. Our results strongly suggest that inhibition of p38 can improve lung oxygenation, prevent pulmonary edema, ameliorate the histologic changes, and improve lung functioning after transplantation.…”

Identification and Functional Characterization of the Soybean GmaPPO12 Promoter Conferring Phytophthora sojae Induced Expression

“…The MYB binding sites have been identified in the parsley PAL1 promoter as the sites of fungal elicitor-inducible DNA–protein interactions [54], and the tobacco PR1a promoter [55]. The MYC recognition sites play a critical role in MYC regulation of innate immune responses against mycobacterial infection [56]. Testing these elements from soybeans is now a priority so that we can design the synthetic promoters that are specific and highly induced by pathogens.…”