Pseudomonas aeruginosa infection augments inflammation through miR-301b repression of c-Myb-mediated immune activation and infiltration.
MicroRNAs (miRNAs) play critical roles in various biological processes, including cell proliferation, development and host defence. However, the molecular mechanism for miRNAs in regulating bacterial-induced inflammation remains largely unclear. Here, we report that miR-301b augments pro-inflammatory response during pulmonary infection, and caffeine suppresses the effect of miR-301b and thereby augments respiratory immunity. LPS treatment or Pseudomonas aeruginosa infection induces miR-301b expression via a TLR4/MyD88/NF-κB pathway. Importantly, caffeine decreases miR-301b expression through negative regulation of the cAMP/PKA/NF-κB axis. Further, c-Myb is identified as a target of miR-301b, which positively modulates anti-inflammatory cytokines IL-4 and TGF-β1, but negatively regulates pro-inflammatory cytokines MIP-1α and IL-17A. Moreover, repression of miR-301b results in increased transcription of c-Myb and elevated levels of neutrophil infiltration, thereby alleviating infectious symptoms in mice. These findings reveal miR-301b as a new controller of inflammatory response by repressing c-Myb function to inhibit the anti-inflammatory response to bacterial infection, representing a novel mechanism for balancing inflammation.
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Xuefeng
X
Li
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Sisi
S
He
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.
Rongpeng
R
Li
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Xikun
X
Zhou
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Shuang
S
Zhang
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.|Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China.
Min
M
Yu
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.
Yan
Y
Ye
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Yongsheng
Y
Wang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Canhua
C
Huang
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA.
Min
M
Wu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007249:Inflammation; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D020556:Neutrophil Infiltration / Q000276:immunology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D020381:Interleukin-17; C573832:MIRN301 microRNA, mouse; D035683:MicroRNAs; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010726:Phosphodiesterase Inhibitors; D020598:Proto-Oncogene Proteins c-myb; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D002110:Caffeine
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