Potential Role of Heme Oxygenase-1 in the Resolution of Experimentally Induced Colitis through Regulation of Macrophage Polarization
- Author:
Shin-Young GWAK
1
;
Su-Jung KIM
;
Jeongmin PARK
;
Seung Hyeon KIM
;
Yeonsoo JOE
;
Ha-Na LEE
;
Wonki KIM
;
Ishrat Aklima MUNA
;
Hye-Kyung NA
;
Hun Taeg CHUNG
;
Young-Joon SURH
Author Information
- Publication Type:Original Article
- From:Gut and Liver 2022;16(2):246-258
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
