PMID- 34390195
OWN - NLM
STAT- MEDLINE
DCOM- 20220328
LR  - 20220328
IS  - 1613-4133 (Electronic)
IS  - 1613-4125 (Linking)
VI  - 65
IP  - 20
DP  - 2021 Oct
TI  - Konjac Glucomannan Oligosaccharides Prevent Intestinal Inflammation Through 
      SIGNR1-Mediated Regulation of Alternatively Activated Macrophages.
PG  - e2001010
LID - 10.1002/mnfr.202001010 [doi]
AB  - SCOPE: Konjac glucomannan oligosaccharides (KMOS) are prebiotics and may improve 
      intestinal immunity through modulation of macrophage function. However, the 
      underlying molecular mechanisms were unclear. METHODS AND RESULTS: Using a mouse 
      model of dextran sulfated sodium (DSS)-induced acute colitis, the study 
      demonstrates here that KMOS (400 mg(-1) kg(-1) d(-1) ) can ameliorate intestinal 
      inflammation in a macrophage dependent manner. Oral exposure to KMOS prevents 
      DSS-induced intestinal pathology, improves epithelial integrity, and decreases 
      accumulation of colonic inflammatory leukocytes and cytokines. The therapeutic 
      effects of KMOS are dependent on the function of macrophages, as depletion of 
      macrophages abolished the effects. In colonic lamina propria of DSS-treated mice, 
      as well as in vitro culture of bone marrow derived macrophages (BMDMs), KMOS 
      skews reprogramming of classically activated macrophages (CAM/M1) into 
      alternatively activated macrophages (AAM/M2). The study further determines that 
      the activation of SIGNR1/phospho-c-Raf (S338)/phospho-p65 (S276)/acetyl-p65 
      (K310) pathway is responsible for KMOS-induced AAM/M2 polarization. Blockage of 
      SIGNR1 abolishes KMOS-induced AAM/M2 polarization of activated macrophages, 
      expression of phospho-p65 (S276) in colonic macrophages, and alleviation of 
      DSS-induced colitis in mice, suggesting that SIGNR1 is critical for macrophage 
      responses to KMOS. CONCLUSIONS: This study reveals a SIGNR1-mediated 
      macrophage-dependent pathway that supports regulatory function of KMOS in host 
      immunity and intestinal homeostasis.
CI  - (c) 2021 Wiley-VCH GmbH.
FAU - Tang, Jiqing
AU  - Tang J
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing, 100083, China.
FAU - Liu, Jun
AU  - Liu J
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing, 100083, China.
FAU - Yan, Qiaojuan
AU  - Yan Q
AD  - Key Laboratory of Food Bioengineering (China National Light Industry), College of 
      Food Science and Nutritional Engineering, China Agricultural University, Beijing, 
      100083, China.
FAU - Gu, Zhenglong
AU  - Gu Z
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing, 100083, China.
AD  - Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA.
FAU - August, Avery
AU  - August A
AD  - Department of Microbiology and Immunology, College of Veterinary Medicine, 
      Cornell University, Ithaca, NY, 13843, USA.
FAU - Huang, Weishan
AU  - Huang W
AD  - Department of Microbiology and Immunology, College of Veterinary Medicine, 
      Cornell University, Ithaca, NY, 13843, USA.
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana 
      State University, Baton Rouge, LA, 70803, USA.
FAU - Jiang, Zhengqiang
AU  - Jiang Z
AUID- ORCID: 0000-0002-9573-2890
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing, 100083, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210825
PL  - Germany
TA  - Mol Nutr Food Res
JT  - Molecular nutrition & food research
JID - 101231818
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannans)
RN  - 0 (Oligosaccharides)
RN  - 0 (Prebiotics)
RN  - 0 (Receptors, Cell Surface)
RN  - 36W3E5TAMG ((1-6)-alpha-glucomannan)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Cell Adhesion Molecules/*physiology
MH  - Colitis/chemically induced/*prevention & control
MH  - Dextran Sulfate
MH  - Lectins, C-Type/*physiology
MH  - Macrophage Activation/drug effects/*physiology
MH  - Male
MH  - Mannans/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligosaccharides/*pharmacology
MH  - *Prebiotics
MH  - Receptors, Cell Surface/*physiology
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - SIGNR1
OT  - intestinal immunity, intestinal inflammation
OT  - konjac glucomannan oligosaccharides
OT  - macrophages
EDAT- 2021/08/15 06:00
MHDA- 2022/03/29 06:00
CRDT- 2021/08/14 06:41
PHST- 2021/08/05 00:00 [revised]
PHST- 2020/10/23 00:00 [received]
PHST- 2021/08/15 06:00 [pubmed]
PHST- 2022/03/29 06:00 [medline]
PHST- 2021/08/14 06:41 [entrez]
AID - 10.1002/mnfr.202001010 [doi]
PST - ppublish
SO  - Mol Nutr Food Res. 2021 Oct;65(20):e2001010. doi: 10.1002/mnfr.202001010. Epub 
      2021 Aug 25.