TY - JOUR
T1 - Proinflammatory Polarization of Macrophages Causes Intestinal Inflammation in Low-Birth-Weight Piglets and Mice
AU - Zhang, Xiangyu
AU - Wu, Yujun
AU - Liu, Xiaoyi
AU - Lin, Xu
AU - Liu, Yisi
AU - Kang, Luyuan
AU - Ye, Hao
AU - Wang, Zhenyu
AU - Ma, Yingying
AU - Dai, Zhaolai
AU - Che, Dongsheng
AU - Pi, Yu
AU - Che, Lianqiang
AU - Wang, Junjun
AU - Han, Dandan
PY - 2023/6
Y1 - 2023/6
N2 - Background: Low-birth-weight (LBW) animals suffer from intestinal damage and inflammation in their early life. Objectives: The aim of this study was to investigate the role of macrophages in intestinal inflammation in LBW piglets and mice. Methods: Major genes involved in intestinal barrier function such as claudin-1, zonula occludens-1 (ZO-1), occludin, and mucin 2 and inflammatory cytokines such as IL-1β, TNF-α, IL-10, and IL-13 were evaluated in 21-day-old, normal-birth-weight (NBW) and LBW piglets and mice. Macrophage markers such as CD16/32, CD163, and CD206 were also assessed by immunofluorescence and flow cytometry. Polarized and unpolarized macrophages were further transferred into NBW and LBW mice, followed by an evaluation of intestinal permeability and inflammation. Results: Claudin-1 mRNA in LBW piglets as well as claudin-1, occludin, ZO-1, and mucin 2 mRNAs in LBW mice, was significantly downregulated. IL-1β and TNF-α were significantly upregulated in LBW piglets (P < 0.05). LBW mice showed a reduced expression of IL-10 and IL-13 (P < 0.05), with a heightened IL-6 level (P < 0.01) in the jejunum. CD16, a marker for M1 macrophages, was significantly elevated in the jejunum of LBW piglets, whereas CD163, a marker for M2 macrophages, was significantly decreased (P < 0.05). Similarly, LBW mice had more CD11b+CD16/32+ M1 macrophages (P < 0.05) and fewer CD206+ M2 macrophages (P < 0.01) than NBW mice. Moreover, the transfer of M1 macrophages exacerbated intestinal inflammation in LBW mice. Furthermore, 2 major glycolysis-associated genes, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), were significantly upregulated in LBW piglets and mice (P < 0.05). Conclusions: This study revealed for the first time that the intestinal macrophages are polarized toward a proinflammatory phenotype in LBW piglets and mice, contributing to intestinal inflammation. The findings of this study provide new options for the management of intestinal inflammation in LBW animals.
AB - Background: Low-birth-weight (LBW) animals suffer from intestinal damage and inflammation in their early life. Objectives: The aim of this study was to investigate the role of macrophages in intestinal inflammation in LBW piglets and mice. Methods: Major genes involved in intestinal barrier function such as claudin-1, zonula occludens-1 (ZO-1), occludin, and mucin 2 and inflammatory cytokines such as IL-1β, TNF-α, IL-10, and IL-13 were evaluated in 21-day-old, normal-birth-weight (NBW) and LBW piglets and mice. Macrophage markers such as CD16/32, CD163, and CD206 were also assessed by immunofluorescence and flow cytometry. Polarized and unpolarized macrophages were further transferred into NBW and LBW mice, followed by an evaluation of intestinal permeability and inflammation. Results: Claudin-1 mRNA in LBW piglets as well as claudin-1, occludin, ZO-1, and mucin 2 mRNAs in LBW mice, was significantly downregulated. IL-1β and TNF-α were significantly upregulated in LBW piglets (P < 0.05). LBW mice showed a reduced expression of IL-10 and IL-13 (P < 0.05), with a heightened IL-6 level (P < 0.01) in the jejunum. CD16, a marker for M1 macrophages, was significantly elevated in the jejunum of LBW piglets, whereas CD163, a marker for M2 macrophages, was significantly decreased (P < 0.05). Similarly, LBW mice had more CD11b+CD16/32+ M1 macrophages (P < 0.05) and fewer CD206+ M2 macrophages (P < 0.01) than NBW mice. Moreover, the transfer of M1 macrophages exacerbated intestinal inflammation in LBW mice. Furthermore, 2 major glycolysis-associated genes, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), were significantly upregulated in LBW piglets and mice (P < 0.05). Conclusions: This study revealed for the first time that the intestinal macrophages are polarized toward a proinflammatory phenotype in LBW piglets and mice, contributing to intestinal inflammation. The findings of this study provide new options for the management of intestinal inflammation in LBW animals.
KW - glycolysis
KW - intestinal barrier
KW - intestinal inflammation
KW - low-birth-weight
KW - macrophage
U2 - 10.1016/j.tjnut.2023.04.016
DO - 10.1016/j.tjnut.2023.04.016
M3 - Article
C2 - 37084872
AN - SCOPUS:85159141711
SN - 0022-3166
VL - 153
SP - 1803
EP - 1815
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 6
ER -