PMID- 31178661
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20211009
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2019
DP  - 2019
TI  - PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse 
      Model of Asthma but Dispensable for Their Differentiation and Function.
PG  - 1656484
LID - 10.1155/2019/1656484 [doi]
LID - 1656484
AB  - Dendritic cells (DCs) are critical in asthma and many other immune diseases. We 
      previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a 
      role in Th2-associated DC function is not clear. In this study, we examined 
      whether PARP-1 is critical for DC differentiation and function using bone marrow 
      progenitors and their migration to the lung in an ovalbumin-based mouse model of 
      asthma. Results show that changes in PARP-1 levels during GM-CSF-induced DC 
      differentiation from bone marrow progenitors were cyclic and appear to be part of 
      an array of changes that included STAT3/STAT5/STAT6/GRAIL/RAD51. Interestingly, 
      PARP-1 gene deletion affected primarily STAT6 and gammaH2AX. PARP-1 inhibition 
      significantly reduced the migration of DCs to the lungs of ovalbumin-challenged 
      mice, which was associated with a concomitant reduction in lung levels of the 
      adhesion molecule VCAM-1. The requirement of PARP-1 for VCAM-1 expression was 
      confirmed using endothelial and lung smooth muscle cells. PARP-1 expression and 
      activity were also required for VCAM-1 in differentiated DCs. An assessment of 
      CD11b(+)/CD11c(+)/MHCII(high) DCs in spleens and lymph nodes of OVA-sensitized 
      mice revealed that PARP-1 inhibition genetically or by olaparib exerted little to 
      no effect on DC differentiation, percentage of CD80(+)/CD86(+)/CD40(+)-expressing 
      cells, or their capacity to promote proliferation of ovalbumin-primed (OTII) 
      CD4(+) T cells. These findings were corroborated using GM-CSF-induced 
      differentiation of DCs from the bone marrow. Surprisingly, the PARP-1(-/-) DCs 
      exhibited a higher intrinsic capacity to induce OTII CD4(+) T cell proliferation 
      in the absence of ovalbumin. Overall, our results show that PARP-1 plays little 
      to no role in DC differentiation and function and that the protective effect of 
      PARP-1 inhibition against asthma is associated with a prevention of DC migration 
      to the lung through a reduction in VCAM-1 expression. Given the current use of 
      PARP inhibitors (e.g., olaparib) in the clinic, the present results may be of 
      interest for the relevant therapies.
FAU - Echeverri Tirado, Laura C
AU  - Echeverri Tirado LC
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
AD  - Grupo de Ciencias Basicas, Escuela de Graduados, Universidad CES, Medellin, 
      Colombia.
FAU - Ghonim, Mohamed A
AU  - Ghonim MA
AUID- ORCID: 0000-0001-9404-2698
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar 
      University, Cairo, Egypt.
FAU - Wang, Jeffrey
AU  - Wang J
AUID- ORCID: 0000-0003-0216-3949
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
FAU - Al-Khami, Amir A
AU  - Al-Khami AA
AUID- ORCID: 0000-0002-9761-9760
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
AD  - Faculty of Science, Tanta University, Tanta, Egypt.
FAU - Wyczechowska, Dorota
AU  - Wyczechowska D
AUID- ORCID: 0000-0002-8940-6861
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
FAU - Luu, Hanh H
AU  - Luu HH
AUID- ORCID: 0000-0001-6123-8774
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
FAU - Kim, Hogyoung
AU  - Kim H
AUID- ORCID: 0000-0002-1834-5133
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
FAU - Sanchez-Pino, Maria Dulfary
AU  - Sanchez-Pino MD
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
FAU - Yelamos, Jose
AU  - Yelamos J
AD  - Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, 
      Spain.
FAU - Yassin, Lina M
AU  - Yassin LM
AUID- ORCID: 0000-0002-9375-0374
AD  - Grupo de Ciencias Basicas, Escuela de Graduados, Universidad CES, Medellin, 
      Colombia.
AD  - Facultad de Medicina, Grupo de Investigaciones Biomedicas Uniremington, 
      Corporacion Universitaria Remington, Medellin, Colombia.
FAU - Boulares, A Hamid
AU  - Boulares AH
AUID- ORCID: 0000-0001-9916-8126
AD  - The Stanley Scott Cancer Center/Louisiana Cancer Research Center, School of 
      Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 
      USA.
LA  - eng
GR  - P30 GM106392/GM/NIGMS NIH HHS/United States
GR  - P30 GM114732/GM/NIGMS NIH HHS/United States
GR  - R01 HL072889/HL/NHLBI NIH HHS/United States
GR  - U54 GM104940/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20190424
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (STAT6 Transcription Factor)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
SB  - IM
MH  - Animals
MH  - Asthma/*metabolism
MH  - Dendritic Cells/*metabolism
MH  - Flow Cytometry
MH  - Lung/*metabolism
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Poly (ADP-Ribose) Polymerase-1/genetics/*metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - STAT5 Transcription Factor/metabolism
MH  - STAT6 Transcription Factor/metabolism
PMC - PMC6507252
EDAT- 2019/06/11 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/04/24
CRDT- 2019/06/11 06:00
PHST- 2018/10/02 00:00 [received]
PHST- 2018/12/15 00:00 [revised]
PHST- 2019/01/02 00:00 [accepted]
PHST- 2019/06/11 06:00 [entrez]
PHST- 2019/06/11 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/04/24 00:00 [pmc-release]
AID - 10.1155/2019/1656484 [doi]
PST - epublish
SO  - Mediators Inflamm. 2019 Apr 24;2019:1656484. doi: 10.1155/2019/1656484. 
      eCollection 2019.