PMID- 36465100
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230116
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 25
IP  - 12
DP  - 2022 Dec 22
TI  - Blockage of lamin-A/C loss diminishes the pro-inflammatory macrophage response.
PG  - 105528
LID - 10.1016/j.isci.2022.105528 [doi]
LID - 105528
AB  - Mutations and defects in nuclear lamins can cause major pathologies, including 
      inflammation and inflammatory diseases. Yet, the underlying molecular mechanisms 
      are not known. We now report that the pro-inflammatory activation of macrophages, 
      as induced by LPS or pathogenic E. coli, reduces Lamin-A/C levels thereby 
      augmenting pro-inflammatory gene expression and cytokine secretion. We show that 
      the activation of bone-marrow-derived macrophages (BMDMs) causes the 
      phosphorylation and degradation of Lamin-A/C, as mediated by CDK1 and Caspase-6, 
      respectively, necessary for upregulating IFN-beta expression. Enhanced IFN-beta 
      expression subsequently increases pro-inflammatory gene expression via the 
      IFN-beta-STAT axis. Pro-inflammatory gene expression was also amplified in the 
      complete absence of Lamin-A/C. Alternatively, pharmacological inhibition of 
      either Lamin-A/C phosphorylation or degradation significantly downregulated 
      pro-inflammatory gene expression, as did the targeting of IFN-beta-STAT pathway 
      members, i.e. phospho-STAT1 and phospho-STAT3. As Lamin-A/C is a previously 
      unappreciated regulator of the pro-inflammatory macrophage response, our findings 
      suggest novel opportunities to treat inflammatory diseases.
CI  - (c) 2022 The Author(s).
FAU - Mehl, Johanna L
AU  - Mehl JL
AD  - Laboratory of Applied Mechanobiology, Institute of Translational Medicine, 
      Department of Health Sciences and Technology, ETH Zurich, Vladimir-Prelog-Weg 
      1-5/10, HCI E357.1, Zurich 8093, Switzerland.
FAU - Earle, Ashley
AU  - Earle A
AD  - Meinig School of Biomedical Engineering & Weill Institute for Cell and Molecular 
      Biology, Cornell University, Ithaca, NY, USA.
AD  - Department of Civil and Mechanical Engineering, York College of Pennsylvania, 
      York, PA, USA.
FAU - Lammerding, Jan
AU  - Lammerding J
AD  - Meinig School of Biomedical Engineering & Weill Institute for Cell and Molecular 
      Biology, Cornell University, Ithaca, NY, USA.
FAU - Mhlanga, Musa
AU  - Mhlanga M
AD  - Radboud Institute of Molecular Life Sciences, Radboud University, Nijmegen, the 
      Netherlands.
FAU - Vogel, Viola
AU  - Vogel V
AD  - Laboratory of Applied Mechanobiology, Institute of Translational Medicine, 
      Department of Health Sciences and Technology, ETH Zurich, Vladimir-Prelog-Weg 
      1-5/10, HCI E357.1, Zurich 8093, Switzerland.
FAU - Jain, Nikhil
AU  - Jain N
AD  - Laboratory of Applied Mechanobiology, Institute of Translational Medicine, 
      Department of Health Sciences and Technology, ETH Zurich, Vladimir-Prelog-Weg 
      1-5/10, HCI E357.1, Zurich 8093, Switzerland.
LA  - eng
GR  - R01 GM137605/GM/NIGMS NIH HHS/United States
GR  - R01 HL082792/HL/NHLBI NIH HHS/United States
GR  - U54 CA210184/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20221107
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC9708799
OTO - NOTNLM
OT  - Cell biology
OT  - Functional aspects of cell biology
OT  - Immune response
OT  - Immunology
COIS- The authors declare that there is no conflict of interest regarding the 
      publication of this article.
EDAT- 2022/12/06 06:00
MHDA- 2022/12/06 06:01
PMCR- 2022/11/07
CRDT- 2022/12/05 03:35
PHST- 2022/04/20 00:00 [received]
PHST- 2022/08/09 00:00 [revised]
PHST- 2022/11/04 00:00 [accepted]
PHST- 2022/12/05 03:35 [entrez]
PHST- 2022/12/06 06:00 [pubmed]
PHST- 2022/12/06 06:01 [medline]
PHST- 2022/11/07 00:00 [pmc-release]
AID - S2589-0042(22)01800-4 [pii]
AID - 105528 [pii]
AID - 10.1016/j.isci.2022.105528 [doi]
PST - epublish
SO  - iScience. 2022 Nov 7;25(12):105528. doi: 10.1016/j.isci.2022.105528. eCollection 
      2022 Dec 22.