Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

Abstract

Trichinella spiralis induced alternative activated macrophages (M2), leading to protect against Crohn’s disease, known as Th1 –related inflammation, which enhances oxidative stress in the host. However, the relationship of oxidative stress and T. spiralis –mediated immune response is still unknown. In our study, we showed that nuclear factor erythroid 2-related factor-2 (Nrf2), a key transcription factor in antioxidant, participated in M2 polarization induced by T. spiralis muscle larval excretory/secretory (ES) products in vitro. ES –treated M2 were injected intravenously after TNBS challenge and we demonstrated that ES-M could alleviate the severity of the colitis in mice. Adoptive transfer of ES –treated M2 decreased the level of IFN-γ and increased the levels of IL-4 and IL-10 in vivo. However, the capacity of ES –treated Nrf2 KO macrophages to treat colitis was dramatically impaired. ES –treated Nrf2 KO macrophages was insufficient to result in the elevated levels of IL-4 and IL-10. These findings indicate that Nrf2 was required for M2 polarization induced by T. spiralis ES to alleviate colitis in mice.

Interleukin-4 Programmed Macrophages Suppress Colitis and Do Not Enhance Infectious-Colitis, Inflammation-Associated Colon Cancer or Airway Hypersensitivity

“…Cellular therapy is an approach to auto-inflammatory disease in which, typically, mesenchymal stem cells or regulatory immune cells are used to blunt inflammation (34,35). Expanding on the ability of macrophages to promote wound healing (3), we showed that murine M(IL4)s reduced disease in three models of chemicalinduced colitis (12)(13)(14); a finding confirmed by others using M(IL4)s or other phenotypes of regulatory macrophage (15)(16)(17)(18)(19). All medications have side effects, and this provided the impetus to determine if the anti-colitic M(IL4) would exacerbate other conditions that can occur in IBD.…”

“…We showed that systemic delivery of in vitro differentiated murine M(IL4)s significantly reduced the severity of dinitrobenzene sulphonic acid (DNBS), oxazolone, and dextran sodium sulphate (DSS) induced colitis in mice: in contrast, the administration of CAMs differentiated in vitro with IFNg [or control M(0)] did not impact the outcome of the colitic disease (12)(13)(14). This anti-colitic effect of murine M(IL4)s and other AAM phenotypes was subsequently supported by other studies (15)(16)(17)(18)(19). In accordance with these findings, it was recently shown that soluble mediators from human M(IL4)s stimulated epithelial (i.e.…”

Targeting Lineage-Specific Transcription Factors and Cytokines of the Th17/Treg Axis by Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Attenuates TNBS-Induced Experimental Colitis

“…Following administration of TNBS solution, as happened in this study, rats develop acute colitis hallmarks, including body weight loss, inconsistent stool formation, diarrhea, and rectal bleeding [ 29 ] used in various scales assessing the severity of inflammatory bowel disease, e.g., DAI score [ 30 ]. The results found in this study revealed that compound 7b given at a dose of 10 or 20 mg/kg and compound 13b at a dose of 20 mg/kg alleviated the course of experimental colitis, as evidenced by improved body weight loss as well as by the reduction in DAI, colon index, and macroscopically visible lesions.…”

“…In addition to body weight changes, stool consistency and blood in the stool were monitored. Based on these three parameters (which are analogous to the clinical presentation of human IBD), the disease activity index (DAI) was calculated as the sum of points ranging from 0 (unaffected) to 12 (severe colitis) scored by evaluation of each parameter following a previously reported scale [ 30 ]. The scoring scale of DAI parameters was as follows: weight loss (%): 0, 0–1%; 1, 1–4%; 2, 4–8%; 3, 8–12%; 4, >12%.…”

Extracellular vesicles derived from Trichinella Spiralis larvae promote the polarization of macrophages to M2b type and inhibit the activation of fibroblasts

“…T. spiralis can be encapsulated in the skeletal muscles of the host, and alternative activated macrophages (M2) play a critical role in T. spiralis infection ( 9 ). To avoid the immune response of the host, the T. spiralis larvae secrete anti-inflammatory substances, such as nuclear factor erythroid 2-related factor-2 ( 10 ), T. spiralis thioredoxin peroxidase-2 ( 11 ), and T. spiralis extracellular vesicles ( 12 ), to reduce the inflammatory response of the host. To coexist with the host for a long time, the secreted products of T. spiralis larvae may have the effect of inhibiting the activation of host fibroblasts.…”