PMID- 34502552
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20240226
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 17
DP  - 2021 Sep 6
TI  - Deletion of Cdk5 in Macrophages Ameliorates Anti-Inflammatory Response during 
      Endotoxemia through Induction of C-Maf and Il-10.
LID - 10.3390/ijms22179648 [doi]
LID - 9648
AB  - Immune response control is critical as excessive cytokine production can be 
      detrimental and damage the host. Interleukin-10 (Il-10), an anti-inflammatory 
      cytokine produced primarily by macrophages, is a key regulator that counteracts 
      and controls excessive inflammatory response. Il-10 expression is regulated 
      through the transcription factor c-Maf. Another regulator of Il-10 production is 
      p35, an activator of the cyclin-dependent kinase 5 (Cdk5), which decreases Il-10 
      production in macrophages, thus increasing inflammation. However, Cdk5 regulation 
      of c-Maf and the involvement of Il-10 production in macrophages has not yet been 
      investigated. We used in vitro primary bone marrow-derived macrophages (BMDMs) 
      lacking Cdk5, stimulated them with lipopolysaccharid (LPS) and observed increased 
      levels of c-Maf and Il-10. In an in vivo mouse model of LPS-induced endotoxemia, 
      mice lacking Cdk5 in macrophages showed increased levels of c-Maf and elevated 
      levels of Il-10 in lungs as well as in plasma, resulting in ameliorated survival. 
      Taken together, we identified Cdk5 as a potential novel regulator of Il-10 
      production through c-Maf in macrophages under inflammatory conditions. Our 
      results suggest that inhibition of Cdk5 enhances the c-Maf-Il-10 axis and thus 
      potentiates improvement of anti-inflammatory therapy.
FAU - Pfander, Pauline
AU  - Pfander P
AD  - Institute of Comparative Molecular Endocrinology (CME), Faculty of Natural 
      Sciences, Ulm University, 89081 Ulm, Germany.
AD  - DKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), Faculty 
      of Bioscience, Heidelberg University, 69120 Heidelberg, Germany.
FAU - Eiers, Ann-Kathrin
AU  - Eiers AK
AD  - Institute of Comparative Molecular Endocrinology (CME), Faculty of Natural 
      Sciences, Ulm University, 89081 Ulm, Germany.
FAU - Burret, Ute
AU  - Burret U
AD  - Institute of Comparative Molecular Endocrinology (CME), Faculty of Natural 
      Sciences, Ulm University, 89081 Ulm, Germany.
FAU - Vettorazzi, Sabine
AU  - Vettorazzi S
AUID- ORCID: 0000-0001-8667-9488
AD  - Institute of Comparative Molecular Endocrinology (CME), Faculty of Natural 
      Sciences, Ulm University, 89081 Ulm, Germany.
LA  - eng
GR  - Project-ID 251293561 - SFB 1149/Deutsche Forschungsgemeinschaft/
GR  - GRK 2203 Pulmosens/Deutsche Forschungsgemeinschaft/
GR  - Bausteinprogramm Universitat Ulm/Start-Up Funding Program of Medical Faculty 
      University Ulm/
PT  - Journal Article
DEP - 20210906
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proto-Oncogene Proteins c-maf)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokines/genetics/metabolism
MH  - Cyclin-Dependent Kinase 5/*genetics/metabolism
MH  - Cytokines/genetics/metabolism
MH  - Endotoxemia/chemically induced/*genetics/metabolism
MH  - Gene Expression Regulation
MH  - Inflammation/*genetics/metabolism
MH  - Interleukin-10/*genetics/metabolism
MH  - Lipopolysaccharides
MH  - Lung/metabolism/pathology
MH  - Macrophages/*metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins c-maf/*genetics/metabolism
MH  - Mice
PMC - PMC8431799
OTO - NOTNLM
OT  - Cdk5
OT  - Il-10
OT  - anti-inflammation
OT  - c-Maf
OT  - macrophage
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/11 06:00
MHDA- 2021/10/26 06:00
PMCR- 2021/09/06
CRDT- 2021/09/10 01:08
PHST- 2021/06/30 00:00 [received]
PHST- 2021/08/27 00:00 [revised]
PHST- 2021/09/02 00:00 [accepted]
PHST- 2021/09/10 01:08 [entrez]
PHST- 2021/09/11 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/09/06 00:00 [pmc-release]
AID - ijms22179648 [pii]
AID - ijms-22-09648 [pii]
AID - 10.3390/ijms22179648 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Sep 6;22(17):9648. doi: 10.3390/ijms22179648.