Limits...
Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution.

Lee WB, Kang JS, Choi WY, Zhang Q, Kim CH, Choi UY, Kim-Ha J, Kim YJ - Nat Commun (2016)

Bottom Line: Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production.In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution.Thus, Mincle has dual functions in the promotion and subsequent resolution of inflammation during anti-mycobacterial defence using both transcriptional and translational controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.

ABSTRACT
In response to persistent mycobacteria infection, the host induces a granuloma, which often fails to eradicate bacteria and results in tissue damage. Diverse host receptors are required to control the formation and resolution of granuloma, but little is known concerning their regulatory interactions. Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production. In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution. Thus, Mincle has dual functions in the promotion and subsequent resolution of inflammation during anti-mycobacterial defence using both transcriptional and translational controls.

No MeSH data available.


Related in: MedlinePlus

Model explaining Mincle-mediated translational regulation for nitric oxide production and inflammation resolution.In this model, Mincle is essential not only for transcription of proinflammatory genes, but also for translation of the key NO synthesis genes. Mincle promotes strong NO release by enhancing iNOS translation via a mechanism dependent on p38-mediated hypusination of eIF5A, inhibiting NLRP3 inflammasome and caspase-1-dependent IL-1β production. ASC, Apoptosis-associated speck-like protein containing a caspase recruitment domain; Hyp, hypusination; SNO, S-nitrosylation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4837483&req=5

f8: Model explaining Mincle-mediated translational regulation for nitric oxide production and inflammation resolution.In this model, Mincle is essential not only for transcription of proinflammatory genes, but also for translation of the key NO synthesis genes. Mincle promotes strong NO release by enhancing iNOS translation via a mechanism dependent on p38-mediated hypusination of eIF5A, inhibiting NLRP3 inflammasome and caspase-1-dependent IL-1β production. ASC, Apoptosis-associated speck-like protein containing a caspase recruitment domain; Hyp, hypusination; SNO, S-nitrosylation.

Mentions: In summary, in addition to the stimulatory effect of Mincle on TLR signalling, our study provides evidence that TDM-induced Mincle signalling promotes the p38- and eIF5A-dependent translational regulation of specific genes including iNOS, which relieve inflammation by inhibiting IL-1β production (Fig. 8). Mincle was initially identified as an activating receptor for inflammation induced by cord factor, well known as an adjuvant. Although Mincle's function in suppressing inflammation is unexpected and initially counterintuitive, our findings demonstrate the pivotal role of Mincle in maintaining balanced immune responses for effective mycobacterial eradication without significant immunopathological damage.


Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution.

Lee WB, Kang JS, Choi WY, Zhang Q, Kim CH, Choi UY, Kim-Ha J, Kim YJ - Nat Commun (2016)

Model explaining Mincle-mediated translational regulation for nitric oxide production and inflammation resolution.In this model, Mincle is essential not only for transcription of proinflammatory genes, but also for translation of the key NO synthesis genes. Mincle promotes strong NO release by enhancing iNOS translation via a mechanism dependent on p38-mediated hypusination of eIF5A, inhibiting NLRP3 inflammasome and caspase-1-dependent IL-1β production. ASC, Apoptosis-associated speck-like protein containing a caspase recruitment domain; Hyp, hypusination; SNO, S-nitrosylation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837483&req=5

f8: Model explaining Mincle-mediated translational regulation for nitric oxide production and inflammation resolution.In this model, Mincle is essential not only for transcription of proinflammatory genes, but also for translation of the key NO synthesis genes. Mincle promotes strong NO release by enhancing iNOS translation via a mechanism dependent on p38-mediated hypusination of eIF5A, inhibiting NLRP3 inflammasome and caspase-1-dependent IL-1β production. ASC, Apoptosis-associated speck-like protein containing a caspase recruitment domain; Hyp, hypusination; SNO, S-nitrosylation.
Mentions: In summary, in addition to the stimulatory effect of Mincle on TLR signalling, our study provides evidence that TDM-induced Mincle signalling promotes the p38- and eIF5A-dependent translational regulation of specific genes including iNOS, which relieve inflammation by inhibiting IL-1β production (Fig. 8). Mincle was initially identified as an activating receptor for inflammation induced by cord factor, well known as an adjuvant. Although Mincle's function in suppressing inflammation is unexpected and initially counterintuitive, our findings demonstrate the pivotal role of Mincle in maintaining balanced immune responses for effective mycobacterial eradication without significant immunopathological damage.

Bottom Line: Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production.In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution.Thus, Mincle has dual functions in the promotion and subsequent resolution of inflammation during anti-mycobacterial defence using both transcriptional and translational controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.

ABSTRACT
In response to persistent mycobacteria infection, the host induces a granuloma, which often fails to eradicate bacteria and results in tissue damage. Diverse host receptors are required to control the formation and resolution of granuloma, but little is known concerning their regulatory interactions. Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production. In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution. Thus, Mincle has dual functions in the promotion and subsequent resolution of inflammation during anti-mycobacterial defence using both transcriptional and translational controls.

No MeSH data available.


Related in: MedlinePlus