PMID- 34737242
OWN - NLM
STAT- MEDLINE
DCOM- 20220414
LR  - 20220428
IS  - 2005-1212 (Electronic)
IS  - 1976-2283 (Print)
IS  - 1976-2283 (Linking)
VI  - 16
IP  - 2
DP  - 2022 Mar 15
TI  - Potential Role of Heme Oxygenase-1 in the Resolution of Experimentally Induced 
      Colitis through Regulation of Macrophage Polarization.
PG  - 246-258
LID - 10.5009/gnl210058 [doi]
AB  - BACKGROUND/AIMS: Heme oxygenase-1 (HO-1) plays a central role in cellular defense 
      against inflammatory insults, and its induction in macrophages potentiates their 
      efferocytic activity. In this study, we explored the potential role of macrophage 
      HO-1 in the resolution of experimentally induced colitis. METHODS: To induce 
      colitis, male C57BL/6 mice were treated with 2% dextran sulfate sodium (DSS) in 
      the drinking water for 7 days. To investigate efferocytosis, apoptotic colon 
      epithelial CCD 841 CoN cells were coincubated with bone marrow-derived 
      macrophages (BMDMs). RESULTS: Administration of the HO-1 inhibitor zinc 
      protoporphyrin IX (ZnPP) blunted the resolution of DSS-induced intestinal 
      inflammation and expression of the proresolving M2 macrophage marker CD206. BMDMs 
      treated with apoptotic colonic epithelial cells showed significantly elevated 
      expression of HO-1 and its regulator Nrf2. Under the same experimental 
      conditions, the proportion of CD206-expressing macrophages was also enhanced. 
      ZnPP treatment abrogated the upregulation of CD206 expression in BMDMs engulfing 
      apoptotic colonic epithelial cells. This result was verified with BMDMs isolated 
      from HO-1-knockout mice. BMDMs, when stimulated with lipopolysaccharide, 
      exhibited increased expression of CD86, a marker of M1 macrophages. Coculture of 
      lipopolysaccharide-stimulated BMDMs with apoptotic colonic epithelial cell debris 
      dampened the expression of CD86 as well as the pro-inflammatory cytokines in an 
      HO-1-dependent manner. Genetic ablation as well as pharmacologic inhibition of 
      HO-1 significantly reduced the proportion of efferocytic BMDMs expressing the 
      scavenger receptor CD36. CONCLUSIONS: HO-1 plays a key role in the resolution of 
      experimentally induced colitis by modulating the polarization of macrophages.
FAU - Gwak, Shin-Young
AU  - Gwak SY
AUID- ORCID: 0000-0002-8988-7087
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul, Korea.
FAU - Kim, Su-Jung
AU  - Kim SJ
AUID- ORCID: 0000-0002-3636-0644
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul 
      National University, Seoul, Korea.
FAU - Park, Jeongmin
AU  - Park J
AUID- ORCID: 0000-0002-3243-7800
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
FAU - Kim, Seung Hyeon
AU  - Kim SH
AUID- ORCID: 0000-0002-9359-7517
AD  - Cancer Research Institute, Seoul National University, Seoul, Korea.
FAU - Joe, Yeonsoo
AU  - Joe Y
AUID- ORCID: 0000-0001-8407-8902
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
FAU - Lee, Ha-Na
AU  - Lee HN
AUID- ORCID: 0000-0001-5063-6689
AD  - Laboratory of Immunology, Division of Biotechnology Review and Research-III, 
      Office of Biotechnology Products, Center for Drug Evaluation and Research, Food 
      and Drug Administration, Silver Spring, MD.
FAU - Kim, Wonki
AU  - Kim W
AUID- ORCID: 0000-0003-0339-7675
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul 
      National University, Seoul, Korea.
FAU - Muna, Ishrat Aklima
AU  - Muna IA
AUID- ORCID: 0000-0003-4384-1611
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul 
      National University, Seoul, Korea.
FAU - Na, Hye-Kyung
AU  - Na HK
AUID- ORCID: 0000-0003-0460-2810
AD  - Department of Food Science and Biotechnology, College of Knowledge-Based Services 
      Engineering, Sungshin Women's University, Seoul, Korea.
FAU - Chung, Hun Taeg
AU  - Chung HT
AUID- ORCID: 0000-0003-4802-7467
AD  - Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
FAU - Surh, Young-Joon
AU  - Surh YJ
AUID- ORCID: 0000-0001-8310-1795
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul, Korea.
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul 
      National University, Seoul, Korea.
AD  - Cancer Research Institute, Seoul National University, Seoul, Korea.
LA  - eng
PT  - Journal Article
PL  - Korea (South)
TA  - Gut Liver
JT  - Gut and liver
JID - 101316452
RN  - 0 (Lipopolysaccharides)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - *Colitis/chemically induced/drug therapy
MH  - Dextran Sulfate
MH  - *Heme Oxygenase-1
MH  - Humans
MH  - Lipopolysaccharides/adverse effects/metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC8924814
OTO - NOTNLM
OT  - Acute colitis
OT  - Dextran sulfate sodium
OT  - Efferocytosis
OT  - Macrophage polarization
OT  - Resolution of inflammation
COIS- CONFLICTS OF INTEREST No potential conflict of interest relevant to this article 
      was reported.
EDAT- 2021/11/06 06:00
MHDA- 2022/04/15 06:00
PMCR- 2021/11/05
CRDT- 2021/11/05 06:04
PHST- 2021/02/05 00:00 [received]
PHST- 2021/05/20 00:00 [revised]
PHST- 2021/05/24 00:00 [accepted]
PHST- 2021/11/06 06:00 [pubmed]
PHST- 2022/04/15 06:00 [medline]
PHST- 2021/11/05 06:04 [entrez]
PHST- 2021/11/05 00:00 [pmc-release]
AID - gnl210058 [pii]
AID - gnl-16-2-246 [pii]
AID - 10.5009/gnl210058 [doi]
PST - ppublish
SO  - Gut Liver. 2022 Mar 15;16(2):246-258. doi: 10.5009/gnl210058.