Dexamethasone increases ROS production and T cell suppressive capacity by anti-inflammatory macrophages

Kraaij, Marina D.; Kooij, Sandra W. van der; Reinders, Marlies E.J.; Koekkoek, Karin; Rabelink, Ton J.; Kooten, Cees van; Gelderman, Kyra A.

doi:10.1016/j.molimm.2011.10.002

Cited by 59 publications

(37 citation statements)

References 34 publications

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“…Impaired T cell immune response has been shown to facilitate infection of the immunocompromised host with intestinal protozoa, however ultimately the pathogenesis within the host is not clearly understood [10]. It is possible that the dexamethasone-induced immunosuppression in these pigs had led to functional pathology such as a dysregulated T cell-mediated immune response [31], [32]. These effects may then allow Blastocystis to colonise not only the usual locations in the large intestine but to also ascend into the distal sections of the small intestine, where it could have a different interaction with the host and potentially cause disease (opportunistic infection).…”

Section: Resultsmentioning

confidence: 99%

Location and Pathogenic Potential of Blastocystis in the Porcine Intestine

et al. 2014

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Blastocystis is an ubiquitous, enteric protozoan of humans and many other species. Human infection has been associated with gastrointestinal disease such as irritable bowel syndrome, however, this remains unproven. A relevant animal model is needed to investigate the pathogenesis/pathogenicity of Blastocystis. We concluded previously that pigs are likely natural hosts of Blastocystis with a potentially zoonotic, host-adapted subtype (ST), ST5, and may make suitable animal models. In this study, we aimed to characterise the host-agent interaction of Blastocystis and the pig, including localising Blastocystis in porcine intestine using microscopy, PCR and histopathological examination of tissues. Intestines from pigs in three different management systems, i.e., a commercial piggery, a small family farm and a research herd (where the animals were immunosuppressed) were examined. This design was used to determine if environment or immune status influences intestinal colonisation of Blastocystis as immunocompromised individuals may potentially be more susceptible to blastocystosis and development of associated clinical signs. Intestines from all 28 pigs were positive for Blastocystis with all pigs harbouring ST5. In addition, the farm pigs had mixed infections with STs 1 and/or 3. Blastocystis organisms/DNA were predominantly found in the large intestine but were also detected in the small intestine of the immunosuppressed and some of the farm pigs, suggesting that immunosuppression and/or husbandry factors may influence Blastocystis colonisation of the small intestine. No obvious pathology was observed in the histological sections. Blastocystis was present as vacuolar/granular forms and these were found within luminal material or in close proximity to epithelial cells, with no evidence of attachment or invasion. These results concur with most human studies, in which Blastocystis is predominantly found in the large intestine in the absence of significant organic pathology. Our findings also support the use of pigs as animal models and may have implications for blastocystosis diagnosis/treatment.

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Section: Resultsmentioning

confidence: 99%

Location and Pathogenic Potential of Blastocystis in the Porcine Intestine

et al. 2014

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“…Tregs play a critical role in the prevention of autoimmunity and resolution of inflammation. Interestingly, the immunosuppressive drug dexamethasone was shown to increase the ability of M2 macrophages to produce ROS, and injection of dexamethasone in rats caused a long-lasting upregulation of ROS production by macrophages and induced higher levels of Tregs in a ROS-dependent manner (57). …”

Section: Discussionmentioning

confidence: 99%

Macrophage Polarization Modulates FcγR- and CD13-Mediated Phagocytosis and Reactive Oxygen Species Production, Independently of Receptor Membrane Expression

Elizabeth

Ortega

2017

Front. Immunol.

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In response to microenvironmental cues, macrophages undergo a profound phenotypic transformation acquiring distinct activation phenotypes ranging from pro-inflammatory (M1) to anti-inflammatory (M2). To study how activation phenotype influences phagocytosis and production of reactive oxygen species (ROS) mediated by receptors for IgG antibodies (Fcγ receptors) and by CD13, human monocyte-derived macrophages were polarized to distinct phenotypes using IFN-γ (Mϕ-IFN-γ), IL-4 (Mϕ-IL-4), or IL-10 (Mϕ-IL-10). Phenotypically, Mϕ-IFN-γ were characterized as CD14+CD80+CD86+ cells, Mϕ-IL-4 as CD209highCD206+CD11b+CD14low, and Mϕ-IL-10 as CD16+CD163+ cells. Compared to non-polarized macrophages, FcγRI expression increased in Mϕ-IFN-γ and Mϕ-IL-10 and FcγRIII expression increased in Mϕ-IL-10. None of the polarizing cytokines modified FcγRII or CD13 expression. Functionally, we found that cytokine-mediated activation significantly and distinctively affected FcγR- and CD13-mediated phagocytosis and ROS generation. Compared to non-polarized macrophages, FcγRI-, FcγRII-, and CD13-mediated phagocytosis was significantly increased in Mϕ-IL-10 and decreased in Mϕ-IFN-γ, although both cytokines significantly upregulated FcγRI expression. IL-10 also increased phagocytosis of Escherichia coli, showing that the effect of IL-10 on macrophage phagocytosis is not specific for a particular receptor. Interestingly, Mϕ-IL-4, which showed poor FcγR- and CD13-mediated phagocytosis, showed very high phagocytosis of E. coli and zymosan. Coupled with phagocytosis, macrophages produce ROS that contribute to microbial killing. As expected, Mϕ-IFN-γ showed significant production of ROS after FcγRI-, FcγRII-, or CD13-mediated phagocytosis. Unexpectedly, we found that Mϕ-IL-10 can also produce ROS after simultaneous stimulation through several phagocytic receptors, as coaggregation of FcγRI/FcγRII/CD13 induced a belated but significant ROS production. Together, these results demonstrate that activation of macrophages by each cytokine distinctly modulates expression of phagocytic receptors, FcγR- and CD13-mediated phagocytosis, and ROS production.

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“…Based on duration of action glucocorticoids are further subcategorised as; short acting (Hydrocortisone, Cortisone), Intermediate acting (Prednisolone, Methylprednisolone) and Long acting (Dexamethasone and Betamethasone) [5]. Dexamethasone has been found effective against the chronic lung disorder in prematurely born infant [6,7], inflammatory [8] and many others disorders. Dexamethasone is being marketed as single API or in combination with other drugs as acetate salt under different brand names.…”

Section: Introductionmentioning

confidence: 99%

Assesment of 28 days repeated adminstration toxicity profile of dexamethasone palmitate injection

Sharma

Rasania

Dadhaniya

et al. 2015

J. Nepal Pharm. Assoc.

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Although, the dexamethasone have been used for the managements, against various ailments as single API or in combination with other drugs as acetate or palmitate salt. However, Dexamethasone as palmitate salt has not been investigated so far for sub acute toxicity on intravenous administration. Therefore, an attempt has been made to investigate sub-acute toxicity of dexamethasone palmitate injection. The drug was administered in experimental animals at different dose levels (0.07, 0.18 and 0.44 mg/kg, b.w.), for 28 days, and alteration in biochemical and haematological parameters was recorded along with histological examinations. The result data revealed that intravenous administration of dexamethasone palmitate does not causes any significant alteration in experimental animals examined at different levels. The observed changes were either well established adverse effects of Dexamethasone or were in laboratory reference range limit. The intravenous administered doses of drug were found safer, although somewhat adverse reactions may be observed at higher dose level (s).

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Dexamethasone increases ROS production and T cell suppressive capacity by anti-inflammatory macrophages

Cited by 59 publications

References 34 publications

Location and Pathogenic Potential of Blastocystis in the Porcine Intestine

Location and Pathogenic Potential of Blastocystis in the Porcine Intestine

Macrophage Polarization Modulates FcγR- and CD13-Mediated Phagocytosis and Reactive Oxygen Species Production, Independently of Receptor Membrane Expression

Assesment of 28 days repeated adminstration toxicity profile of dexamethasone palmitate injection

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