PMID- 36018422
OWN - NLM
STAT- MEDLINE
DCOM- 20230531
LR  - 20230620
IS  - 1572-8773 (Electronic)
IS  - 0966-0844 (Print)
IS  - 0966-0844 (Linking)
VI  - 36
IP  - 3
DP  - 2023 Jun
TI  - Lactoferrin and its digestive peptides induce interferon-alpha production and 
      activate plasmacytoid dendritic cells ex vivo.
PG  - 563-573
LID - 10.1007/s10534-022-00436-y [doi]
AB  - Plasmacytoid dendritic cells (pDCs) recognise viral single-stranded RNA (ssRNA) 
      or CpG DNA via Toll-like receptor (TLR)-7 and TLR9, and produce interferon 
      (IFN)-alpha. Activated pDCs upregulate human leukocyte antigen (HLA)-DR and CD86 
      expression levels. Ingestion of bovine lactoferrin (LF) activates pDCs, but 
      little is known about its effects. In this study, the effects of LF and its 
      pepsin hydrolysate (LFH) on the production of IFN-alpha from peripheral blood 
      mononuclear cells (PBMCs) and pDCs were examined. PBMCs were prepared from 
      peripheral blood of healthy adults and incubated with LF, LFH, or lactoferricin 
      (LFcin) in the absence or presence of ssRNA derived from human immunodeficiency 
      virus. The concentration of IFN-alpha in the supernatant and the expression levels of 
      IFN-alpha, HLA-DR, and CD86 in pDCs were quantified by enzyme-linked immunosorbent 
      assay and flow cytometry. In the absence of ssRNA, the concentration of IFN-alpha was 
      negligible and LF had no effect on it. In the presence of ssRNA, IFN-alpha was 
      detected at a certain level, and LF and LFH significantly increased its 
      concentration. The increase caused by LFH and LFcin were comparable. In addition, 
      LF significantly upregulated the expression levels of IFN-alpha, HLA-DR, and CD86 in 
      pDCs. LF and its digestive peptides induced IFN-alpha production and activated pDCs 
      in the presence of ssRNA, suggesting that LF modulates the immune system by 
      promoting pDC activation upon viral recognition.
CI  - (c) 2022. The Author(s).
FAU - Kubo, Shutaro
AU  - Kubo S
AD  - Food Ingredients and Technology Institute, R&D Division, Morinaga Milk Industry 
      Co., Ltd., 1-83, 5, Higashihara, Zama, Kanagawa, Japan. 
      shuutarou-kubo023@morinagamilk.co.jp.
FAU - Miyakawa, Momoko
AU  - Miyakawa M
AD  - Food Ingredients and Technology Institute, R&D Division, Morinaga Milk Industry 
      Co., Ltd., 1-83, 5, Higashihara, Zama, Kanagawa, Japan.
FAU - Tada, Asuka
AU  - Tada A
AD  - Food Ingredients and Technology Institute, R&D Division, Morinaga Milk Industry 
      Co., Ltd., 1-83, 5, Higashihara, Zama, Kanagawa, Japan.
FAU - Oda, Hirotsugu
AU  - Oda H
AD  - Food Ingredients and Technology Institute, R&D Division, Morinaga Milk Industry 
      Co., Ltd., 1-83, 5, Higashihara, Zama, Kanagawa, Japan.
FAU - Motobayashi, Hideki
AU  - Motobayashi H
AD  - Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, 
      Wakayama, Wakayama, Japan.
FAU - Iwabuchi, Sadahiro
AU  - Iwabuchi S
AD  - Department of Molecular Pathophysiology, Wakayama Medical University, 811-1 
      Kimiidera, Wakayama, Wakayama, Japan.
FAU - Tamura, Shinobu
AU  - Tamura S
AD  - Department of Hematology/Oncology, Wakayama Medical University, 811-1 Kimiidera, 
      Wakayama, Wakayama, Japan.
FAU - Tanaka, Miyuki
AU  - Tanaka M
AD  - Food Ingredients and Technology Institute, R&D Division, Morinaga Milk Industry 
      Co., Ltd., 1-83, 5, Higashihara, Zama, Kanagawa, Japan.
FAU - Hashimoto, Shinichi
AU  - Hashimoto S
AD  - Department of Molecular Pathophysiology, Wakayama Medical University, 811-1 
      Kimiidera, Wakayama, Wakayama, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220826
PL  - Netherlands
TA  - Biometals
JT  - Biometals : an international journal on the role of metal ions in biology, 
      biochemistry, and medicine
JID - 9208478
RN  - 0 (Interferon-alpha)
RN  - EC 3.4.21.- (Lactoferrin)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Dendritic Cells/immunology/metabolism
MH  - Interferon-alpha/metabolism/pharmacology
MH  - *Lactoferrin/pharmacology/metabolism
MH  - *Leukocytes, Mononuclear
PMC - PMC10181974
OTO - NOTNLM
OT  - CD86
OT  - HLA-DR
OT  - Interferon (IFN)
OT  - Lactoferricin
OT  - Lactoferrin
OT  - Plasmacytoid dendritic cells (pDCs)
COIS- This research was conducted by the Morinaga Milk Industry, Japan and Wakayama 
      Medical University, Japan. S.K., M.M., A.T., H.O., and M.T. are employees of the 
      Morinaga Milk Industry. H.M., S.I., S.T., and S.H. declare no conflicts of 
      interest.
EDAT- 2022/08/27 06:00
MHDA- 2023/05/15 06:42
PMCR- 2022/08/26
CRDT- 2022/08/26 11:18
PHST- 2022/05/12 00:00 [received]
PHST- 2022/08/15 00:00 [accepted]
PHST- 2023/05/15 06:42 [medline]
PHST- 2022/08/27 06:00 [pubmed]
PHST- 2022/08/26 11:18 [entrez]
PHST- 2022/08/26 00:00 [pmc-release]
AID - 10.1007/s10534-022-00436-y [pii]
AID - 436 [pii]
AID - 10.1007/s10534-022-00436-y [doi]
PST - ppublish
SO  - Biometals. 2023 Jun;36(3):563-573. doi: 10.1007/s10534-022-00436-y. Epub 2022 Aug 
      26.