Proteomics

Dataset Information

0

CTRP6 promotes macrophage inflammatory response and its deficiency attenuates LPS-induced inflammation


ABSTRACT: Macrophages play critical roles in inflammation and tissue homeostasis, and their functions are regulated by various autocrine, paracrine, and endocrine factors. We have previously shown that CTRP6, a secreted protein of the C1q family, targets both adipocytes and macrophages to promote obesity-linked inflammation in adipose tissue. However, the gene programs and signaling pathways directly regulated by CTRP6 in macrophage remain unknown. Here, we combine transcriptomic and phosphoproteomic analyses to show that CTRP6 activates inflammatory gene programs and signaling pathways in bone marrow-derived macrophages (BMDMs). Treatment of BMDMs with CTRP6 upregulates proinflammatory, and suppresses the anti-inflammatory, gene expression. We show that CTRP6 activates p44/42-MAPK, p38-MAPK, and NF-κB signalings to promote inflammatory cytokine secretion from BMDMs, and that pharmacologic inhibition of these signaling pathways largely abolish the effects of CTRP6. Pretreatment of BMDMs with CTRP6 further augments LPS-induced inflammatory signaling and cytokine secretion from BMDMs. Consistent with the metabolic phenotype of proinflammatory M1-like macrophages, CTRP6 treatment induces a shift toward aerobic glycolysis and lactate production, reduces oxidative metabolism, and elevates mitochondrial ROS production in BMDMs. We use a Ctrp6 knockout mouse model to further confirm the physiologic relevance of our in vitro findings. BMDMs from CTRP6-deficient mice are less inflammatory at baseline and show a marked suppression of LPS-induced inflammatory gene expression and cytokine secretion. Loss of CTRP6 in mice also dampens LPS-induced inflammation and hypothermia. Collectively, we provide mechanistic evidence that CTRP6 regulates macrophage function, and neutralizing CTRP6 activity may have beneficial effects in reducing inflammation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow, Macrophage

SUBMITTER: Jun Zhong  

LAB HEAD: G. William Wong

PROVIDER: PXD042268 | Pride | 2024-01-26

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Phospho_TMT6_Gel.msf Msf
Phospho_TMT6_Gel.mzML Mzml
Phospho_TMT6_Gel_0424_F01.raw Raw
Phospho_TMT6_Gel_0424_F02.raw Raw
Phospho_TMT6_Gel_0424_F03.raw Raw
Items per page:
1 - 5 of 29
altmetric image

Publications

CTRP6 promotes the macrophage inflammatory response, and its deficiency attenuates LPS-induced inflammation.

Xu Cheng C   Sarver Dylan C DC   Lei Xia X   Sahagun Ageline A   Zhong Jun J   Na Chan Hyun CH   Rudich Assaf A   Wong G William GW  

The Journal of biological chemistry 20231214 1


Macrophages play critical roles in inflammation and tissue homeostasis, and their functions are regulated by various autocrine, paracrine, and endocrine factors. We have previously shown that CTRP6, a secreted protein of the C1q family, targets both adipocytes and macrophages to promote obesity-linked inflammation. However, the gene programs and signaling pathways directly regulated by CTRP6 in macrophages remain unknown. Here, we combine transcriptomic and phosphoproteomic analyses to show that  ...[more]

Similar Datasets

2018-01-08 | PXD003092 | Pride
2016-01-26 | PXD002735 | Pride
2019-12-18 | PXD007785 | Pride
2016-05-12 | E-GEOD-71263 | biostudies-arrayexpress
2024-10-15 | GSE267563 | GEO
2024-10-15 | GSE267516 | GEO
2016-12-14 | PXD003108 | Pride
2021-11-15 | E-MTAB-10501 | biostudies-arrayexpress
2023-09-19 | MTBLS6502 | MetaboLights
2018-05-15 | PXD008726 | Pride