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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Analysis of Variance
-
Antibodies, Monoclonal / immunology
-
Blotting, Western
-
Cell Line
-
Colony Count, Microbial
-
Cytoplasm / metabolism
-
DNA Primers / genetics
-
Humans
-
Immunity, Innate / immunology*
-
Immunohistochemistry
-
Interleukin-1 Receptor-Associated Kinases / metabolism*
-
Leukocytes, Mononuclear
-
MAP Kinase Signaling System / immunology*
-
Mycobacterium / immunology*
-
Mycobacterium Infections / immunology*
-
Plasmids / genetics
-
Proto-Oncogene Proteins c-myc / immunology*
-
RNA, Small Interfering / genetics
-
Real-Time Polymerase Chain Reaction
-
Reverse Transcriptase Polymerase Chain Reaction
-
Species Specificity
-
Tetrazolium Salts
-
Thiazoles
Substances
-
Antibodies, Monoclonal
-
DNA Primers
-
MYC protein, human
-
Proto-Oncogene Proteins c-myc
-
RNA, Small Interfering
-
Tetrazolium Salts
-
Thiazoles
-
IRAK1 protein, human
-
Interleukin-1 Receptor-Associated Kinases
-
thiazolyl blue