PMID- 38368463
OWN - NLM
STAT- MEDLINE
DCOM- 20240219
LR  - 20240408
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Feb 17
TI  - Bone marrow stromal cell-derived hepcidin has antimicrobial and immunomodulatory 
      activities.
PG  - 3986
LID - 10.1038/s41598-024-54227-1 [doi]
LID - 3986
AB  - Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous 
      species and have been used in clinical trials. BMSCs also make antibacterial 
      agents. Since hepcidin is known to have antimicrobial effects in fish, we 
      wondered if it might also be used as an antimicrobial agent by mammalian BMSCs. 
      In the present study, we show hepcidin expression in both mouse (mBMSC) and human 
      BMSCs (hBMSC). We observed a hBMSC hepcidin-dependent degradation of ferroportin 
      in HEK-293 reporter cells in vitro. In human and mouse bone marrows (BM) we 
      detected hepcidin-positive BMSCs in close proximity to hematopoietic progenitors. 
      The conditioned culture medium of hBMSCs significantly reduced bacterial 
      proliferation that was partially blocked by a hepcidin-neutralizing antibody. 
      Similarly, medium in which hepcidin-deficient (Hamp(-/-)) mouse BMSCs had been 
      grown was significantly less effective in reducing bacterial counts than the 
      medium of wild-type cells. In a zymosan-induced peritonitis mouse model we found 
      that mBMSC-derived hepcidin reduced the number of invading polymorphonuclear 
      (PMN) cells in the peritoneal cavity. Our results show that BMSC-derived hepcidin 
      has antimicrobial properties in vitro and also reduces inflammation in vivo. We 
      conclude that hepcidin should be added to the expanding arsenal of agents 
      available to BMSCs to fight infections and inflammation.
CI  - (c) 2024. The Author(s).
FAU - Krepuska, Miklos
AU  - Krepuska M
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
AD  - Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland.
FAU - Mayer, Balazs
AU  - Mayer B
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
AD  - Stem Cell Laboratory, Department of Dermatology, Venereology and 
      Dermato-Oncology, Semmelweis University, Budapest, Hungary.
FAU - Vitale-Cross, Lynn
AU  - Vitale-Cross L
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
FAU - Myneni, Vamsee D
AU  - Myneni VD
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
FAU - Boyajian, Michael K
AU  - Boyajian MK
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
FAU - Nemeth, Krisztian
AU  - Nemeth K
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
AD  - Stem Cell Laboratory, Department of Dermatology, Venereology and 
      Dermato-Oncology, Semmelweis University, Budapest, Hungary.
FAU - Szalayova, Ildiko
AU  - Szalayova I
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
FAU - Cho, Ted
AU  - Cho T
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
FAU - McClain-Caldwell, Ian
AU  - McClain-Caldwell I
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
FAU - Gingerich, Aaron D
AU  - Gingerich AD
AD  - Department of Infectious Diseases, College of Veterinary Medicine, University of 
      Georgia, Athens, GA, USA.
FAU - Han, Huiling
AU  - Han H
AD  - Intrinsic Life Sciences, La Jolla, CA, USA.
FAU - Westerman, Mark
AU  - Westerman M
AD  - Intrinsic Life Sciences, La Jolla, CA, USA.
FAU - Rada, Balazs
AU  - Rada B
AD  - Department of Infectious Diseases, College of Veterinary Medicine, University of 
      Georgia, Athens, GA, USA. radab@uga.edu.
FAU - Mezey, Eva
AU  - Mezey E
AD  - National Institutes of Health, NIDCR, ASCS, Bethesda, MD, USA.
LA  - eng
GR  - ZIA CL002120/ImNIH/Intramural NIH HHS/United States
GR  - ZIA DE000714/ImNIH/Intramural NIH HHS/United States
GR  - ZIB DE000730/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20240217
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Hepcidins)
RN  - 0 (Anti-Infective Agents)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Hepcidins/metabolism
MH  - HEK293 Cells
MH  - *Mesenchymal Stem Cells
MH  - *Anti-Infective Agents/pharmacology
MH  - Inflammation/metabolism
MH  - Bone Marrow Cells
MH  - Mammals
PMC - PMC10874407
COIS- The authors declare no competing interests.
EDAT- 2024/02/18 00:42
MHDA- 2024/02/19 06:42
PMCR- 2024/02/17
CRDT- 2024/02/17 23:27
PHST- 2023/08/18 00:00 [received]
PHST- 2024/02/09 00:00 [accepted]
PHST- 2024/02/19 06:42 [medline]
PHST- 2024/02/18 00:42 [pubmed]
PHST- 2024/02/17 23:27 [entrez]
PHST- 2024/02/17 00:00 [pmc-release]
AID - 10.1038/s41598-024-54227-1 [pii]
AID - 54227 [pii]
AID - 10.1038/s41598-024-54227-1 [doi]
PST - epublish
SO  - Sci Rep. 2024 Feb 17;14(1):3986. doi: 10.1038/s41598-024-54227-1.