Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

Bhattacharya, Palash; Budnick, Isadore; Singh, Mukti; Thiruppathi, Muthusamy; Alharshawi, Khaled; Elshabrawy, Hatem A.; Holterman, Mark J.; Prabhakar, Bellur S.

doi:10.1089/jir.2014.0149

Cited by 202 publications

(169 citation statements)

References 182 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…MCP-1 was found to be higher in T1D cases (44). As an immune modulatory cytokine, GM-CSF could exacerbate autoimmune diseases in inflammatory microenvironments (45). IFN-γ induces pancreatic β cell apoptosis through STAT1-mediated Bim protein activation and exacerbates T1D (46).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genistein prevention of hyperglycemia and improvement of glucose tolerance in adult non-obese diabetic mice are associated with alterations of gut microbiome and immune homeostasis

Huang¹,

Xu²,

Lefever³

et al. 2017

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Although studies have linked soy phytoestrogen 4,7,4-trihydroxyisoflavone genistein (GEN) to reduced type 1 diabetes (T1D) risk, the mechanism of dietary GEN on T1D remains unknown. In our studies, adult non-obese diabetic (NOD) mouse model was employed to investigate the effects of GEN exposure on blood glucose level (BGL), glucose tolerance, gut microbiome, and immune responses. Adult male and female NOD mice were fed with either soy-based or casein-based diet, and received GEN at 20 mg/kg body weight by gavage daily. The BGL and immune responses (represented by serum antibodies, cytokines and chemokines, and histopathology) were monitored, while the fecal gut microbiome was sequenced for 16S ribosomal RNA to reveal any alterations in gut microbial communities. A significantly reduced BGL was found in NOD males fed with soy-based diet on day 98 after initial dosing and an improved glucose tolerance was observed on both diets. In addition, an anti-inflammatory response (suggested by reduced IgG2b and cytokine/chemokine levels, and alterations in the microbial taxonomy) was accompanied by an altered β-diversity in gut microbial species. Among the NOD females exposed to GEN, a later onset of T1D was observed. However, the profiles of gut microbiome, antibodies and cytokines/chemokines were all indicative of pro-inflammation This study demonstrated an association among GEN exposure, gut microbiome alteration, and immune homeostasis in NOD males. Although the mechanisms underlying the protective effects of GEN in NOD mice need to be explored further, the current study suggested a GEN-induced sex-specific effect in inflammatory status and gut microbiome.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The protective effect of GEN on T1D in NOD females could be due to direct inhibition of insulitis, increased insulin receptor expression (45) or up-regulation of hepatic glucose-6-phosphate dehydrogenase (G6PD) activities (9). However, these effects were observed in both females (9) and males (14).…”

Section: Discussionmentioning

confidence: 99%

Genistein prevention of hyperglycemia and improvement of glucose tolerance in adult non-obese diabetic mice are associated with alterations of gut microbiome and immune homeostasis

Huang¹,

Xu²,

Lefever³

et al. 2017

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

show abstract

“…GM-CSF is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations23. GM-CSF-mediated inflammation has been implicated in some types of autoimmune diseases, including RA24.…”

Section: Discussionmentioning

confidence: 99%

IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner

Liú

Cao²,

Wang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

IL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4+ T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.

show abstract

“…Granulocyte-macrophage colony-stimulating factor The haematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) is produced by different cell types, including epithelial cells and macrophages, and exerts immune regulatory effects depending on the dose, presence of other cytokines and the overall context of the immune response (reviewed in [35]). GM-CSF treatment reversed sepsis-associated immunosuppression and improved clinical courses in sepsis patients [36].…”

Section: Complement Inhibitorsmentioning

confidence: 99%

Therapeutic strategies in pneumonia: going beyond antibiotics

et al. 2015

View full text Add to dashboard Cite

Dysregulation of the innate immune system drives lung injury and its systemic sequelae due to breakdown of vascular barrier function, harmful hyperinflammation and microcirculatory failure, which contribute to the unfavourable outcome of patients with severe pneumonia. A variety of promising therapeutic targets have been identified and numerous innovative therapeutic approaches demonstrated to improve lung injury in experimental preclinical studies. However, at present specific preventive or curative strategies for the treatment of lung failure in pneumonia in addition to antibiotics are still missing. The aim of this mini-review is to give a short overview of some, but not all, adjuvant therapeutic strategies for pneumonia and its most important complications, sepsis and acute respiratory distress syndrome, and briefly discuss future perspectives. @ERSpublications A review of preclinical and clinical research on adjuvant therapies for pneumonia

show abstract

Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

Cited by 202 publications

References 182 publications

Genistein prevention of hyperglycemia and improvement of glucose tolerance in adult non-obese diabetic mice are associated with alterations of gut microbiome and immune homeostasis

Genistein prevention of hyperglycemia and improvement of glucose tolerance in adult non-obese diabetic mice are associated with alterations of gut microbiome and immune homeostasis

IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner

Therapeutic strategies in pneumonia: going beyond antibiotics

Contact Info

Product

Resources

About