Heme Oxygenase-1 Expressed Macrophages Inhibit Intestinal Inflammation

• Published in: Digestive diseases and sciences 2022-05, Vol.59 (8), p.1660
• Main Authors: Naito, Y, Higashimura, Y, Mizushima, K, Katada, K, Takagi, T
• Format: Article
• Language: English
• Subjects: Enzymes; Gastrointestinal system; Heme; Inflammation; Macrophages
• ISSN: 0163-2116
• DOI: 10.1007/s10620-014-3278-0

Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). HO-1 is a stress-responsive protein induced by various oxidative agents. Recent studies demonstrate that the expression of HO-1 in response to different inflammatory mediators may contribute to the resolution of inflammation and has protective effects in several organs against oxidative injury. Although the mechanism underlying the anti-inflammatory actions of HO-1 remains poorly defined, both CO and biliverdin/bilirubin have been implicated in this response. In the gastrointestinal tract, HO-1 is shown to be transcriptionally induced in response to oxidative stress, preconditioning and acute inflammation. We have demonstrated that the deficiency of Bach1, a negative transcriptional repressor of HO-1, significantly attenuates colonic inflammation induced by trinitrobenzene sulfonic acid (TNBS), and showed that HO-1 is mainly localized in macrophages, regarded as M2-type macrophages. In addition, adoptive transfer of macrophages from Bach1-deficient mice significantly ameliorated the TNBS-induced inflammation in wild type mice. These data suggest that HO-1 may be a novel therapeutic target in patients with gastrointestinal diseases. The next experiment has shown that zinc sulfate (ZnSO4) inhibits TNBS-colitis and that ZnSO4 enhances the surface expression of Fizz-1 and MRC1, markers forM2-type macrophages, as well as HO-1 expression in RAW264 cells. In this session, we will introduce that HO-1 high-expression M2 macrophages are the potential targets of intestinal anti-inflammatory therapy.