PMID- 33453508
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20210625
IS  - 1090-2163 (Electronic)
IS  - 0008-8749 (Linking)
VI  - 361
DP  - 2021 Mar
TI  - Differential signaling patterns of stimulated bone marrow-derived dendritic cells 
      under alpha1-antitrypsin-enriched conditions.
PG  - 104281
LID - S0008-8749(20)30441-X [pii]
LID - 10.1016/j.cellimm.2020.104281 [doi]
AB  - Dendritic cells (DCs) mature upon an inflammatory trigger. However, an 
      inflammatory trigger can lead to a semi-mature phenotype, allowing DCs to evoke 
      tolerance and expedite the resolution of inflammation. This duality likely 
      involves context-dependent modulation of inflammatory signaling. Human 
      alpha1-antitrypsin (hAAT) promotes semimature DCs. We examined changes in a wide 
      spectrum of signaling cascades in stimulated murine bone marrow-derived cells 
      with hAAT. Upon stimulation by IL-1beta+IFNgamma, hAAT-treated cells depicted an 
      attenuated calcium flux. Disrupting PKA or NF-kappaB pathways revoked only some 
      hAAT-mediated outcomes. hAAT-treated cells exhibited a distict pattern of kinase 
      phosphorylation. hAAT-mediated increase in Treg cells in-vitro required intact 
      inflammatory signaling pathways. Taken together, hAAT appears to require a 
      stimulated microenvironment to promote inflammatory resolution, setting it aside 
      from classical anti-inflammatory agents. Further studies are required to identify 
      the specific molecules targeted by hAAT that mediate these and other outcomes.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Ozeri, Eyal
AU  - Ozeri E
AD  - Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Be'er Sheva, Israel.
FAU - Rider, Peleg
AU  - Rider P
AD  - Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Be'er Sheva, Israel.
FAU - Rigbi, Shoham
AU  - Rigbi S
AD  - Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Be'er Sheva, Israel.
FAU - Shahaf, Galit
AU  - Shahaf G
AD  - Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Be'er Sheva, Israel.
FAU - Nita, Iulia I
AU  - Nita II
AD  - Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion 
      University of the Negev, Be'er Sheva, Israel.
FAU - Sekler, Israel
AU  - Sekler I
AD  - Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion 
      University of the Negev, Be'er Sheva, Israel.
FAU - Lewis, Eli C
AU  - Lewis EC
AD  - Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Be'er Sheva, Israel.
FAU - Schuster, Ronen
AU  - Schuster R
AD  - Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Be'er Sheva, Israel. Electronic address: 
      ronensc@post.bgu.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210101
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (alpha 1-Antitrypsin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Bone Marrow/metabolism
MH  - Bone Marrow Cells/metabolism
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/*metabolism
MH  - Immune Tolerance/immunology
MH  - Inflammation/metabolism
MH  - Interleukin-1/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Receptors, CCR7/immunology/metabolism
MH  - Receptors, Interleukin-1/antagonists & inhibitors/immunology
MH  - Signal Transduction/*drug effects/immunology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - alpha 1-Antitrypsin/metabolism/*pharmacology
OTO - NOTNLM
OT  - CCR7
OT  - Calcium signaling
OT  - IL-1 receptor antagonist
OT  - Immunomodulation
OT  - NF-kappaB
EDAT- 2021/01/17 06:00
MHDA- 2021/06/29 06:00
CRDT- 2021/01/16 20:10
PHST- 2020/01/31 00:00 [received]
PHST- 2020/07/17 00:00 [revised]
PHST- 2020/11/21 00:00 [accepted]
PHST- 2021/01/17 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/01/16 20:10 [entrez]
AID - S0008-8749(20)30441-X [pii]
AID - 10.1016/j.cellimm.2020.104281 [doi]
PST - ppublish
SO  - Cell Immunol. 2021 Mar;361:104281. doi: 10.1016/j.cellimm.2020.104281. Epub 2021 
      Jan 1.