Insulin induces monocytic CXCL8 secretion by the mitogenic signalling pathway

Wurm, Simone; Neumeier, Markus; Weigert, Johanna; Wanninger, Josef; Gerl, Melanie; Gindner, Antonia; Schäffler, Andréas; Aslanidis, Charalampos; Schölmerich, Jürgen; Buechler, Christa

doi:10.1016/j.cyto.2008.08.003

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…Similarly, Dimitriadis et al 47 have shown in human studies that high insulin resulted in thereduction of infiltration and accumulation of macrophages in the tissues. Other investigators 45,46 have shown that insulin exerts anti-inflammatory activity by inhibiting the secretion pro-inflammatory cytokines IL-1β, IL-8 and TNF-α. Based on studies cited above 44,45,47 , we can state that insulin treatment in T2D patients, in the present study, might contribute to low numberof total lymphocytes (CD3+ and CD8+ T cells) and high frequency of Treg cells which might be related to low cell-mediated adaptive immunity in these patients, since Treg cells are known to suppress the activation of CD4+ and CD8+ T cells 15,16,27,28 .…”

Section: Discussionmentioning

confidence: 99%

“…Be that as it may, our study shown increased frequencies of Treg cells in T2D patients and, this is consistent with anti-inflammatory profile of these patients and might be partially explained by their insulin treatment. Indeed, it has been well established that insulin exerts anti-inflammatory activity through the inhibition of the production of proinflammatory cytokines by macrophages [44][45][46] . It is thus interesting to observe that insulin-treated T2D patients have shown decreased levels of pro-inflammatory Th1 cytokines (IL-2/IFN-γ).…”

Section: Discussionmentioning

confidence: 99%

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Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Nekoua¹,

Fachinan²,

Atchamou³

et al. 2016

Afr H. Sci.

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Background: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. Objectives:We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). Methods: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed. Results: T2DP were hyperglycemic and showed high level of insulin, normal levels of triglycerides and total-cholesterol and without any change in HDL-cholesterol.Compared to healthy subjects, T2DP exhibited significant decreased frequencies of neutrophils, without any change in monocytes, eosinophils and natural killer cells. The percentages of total lymphocytes (CD3+) and CD8+-T-cells decreased whereas those of regulatory T-cells increased without any change in CD4+ T-cells in T2DP. Interestingly, the frequencies of effector CD4+-T and B-cells increased in T2DP. Serum concentrations of IL-2, IFN-γ and IL-4 decreased while IL-10 significantly enhanced in T2DP, suggesting a differentiation of CD4+T helper cells towards IL-10-producing-Teff-cells in these patients. Conclusion: Insulin-treated type 2 diabetes is associated with anti-inflammatory profile consistent with differentiation of CD4+-Th-cells towards IL-10-producing-Teff-cells, concomitant with increased frequencies of Treg and B-cells, and this may probably offer prevention against certain infections or autoimmune/inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Nekoua¹,

Fachinan²,

Atchamou³

et al. 2016

Afr H. Sci.

View full text Add to dashboard Cite

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“…Production of IL-8 has been assessed in several cell type upon stimulation, several medical conditions and even constitutively [35], [36], [37]. The observed high levels of circulatory IL-8 may mediate desensitization and/or down-regulation of CXCR2 in acutely infected malaria patients.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Paralysis in Plasmodium vivax Malaria

et al. 2012

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Background The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects. Here, we examined the activation and function of neutrophils during acute episodes of malaria. Materials and Methods Blood samples were collected from P. vivax -infected patients at admission (day 0) and 30–45 days after treatment with chloroquine and primaquine. Expression of activation markers and cytokine levels produced by highly purified monocytes and neutrophils were measured by the Cytometric Bead Assay. Phagocytic activity, superoxide production, chemotaxis and the presence of G protein-coupled receptor (GRK2) were also evaluated in neutrophils from malaria patients. Principal Findings Both monocytes and neutrophils from P. vivax -infected patients were highly activated. While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production. Interestingly, neutrophils from the malaria patients expressed high levels of GRK2, low levels of CXCR2, and displayed impaired chemotaxis towards IL-8 (CXCL8). Conclusion Activated neutrophils from malaria patients are a poor source of pro-inflammatory cytokines and display reduced chemotactic activity, suggesting a possible mechanism for an enhanced susceptibility to secondary bacterial infection during malaria.

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“…The MAPK pathway is constitutively activated in most melanomas and plays a major role in mediating the survival and progression of melanoma [50] , [51] . In addition, p38 MAPK [52] , JNK [53] , and ERK [54] are involved in the regulation of IL8 expression in a variety of cell types. HPSE could promote phosphorylation of signaling molecules such as Akt and Src, facilitating gene transcription and phosphorylation of selected Src substrates [43] , [55] , whereas HPSE silencing was accompanied by reduced EGFR and Src phosphorylation levels [56] .…”

Section: Discussionmentioning

confidence: 99%

An Artificial miRNA against HPSE Suppresses Melanoma Invasion Properties, Correlating with a Down-Regulation of Chemokines and MAPK Phosphorylation

et al. 2012

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Ribonucleic acid interference (RNAi) based on microRNA (miRNA) context may provide an efficient and safe therapeutic knockdown effect and can be driven by ribonucleic acid polymerase II (RNAP II). In this study, we designed and synthesized miR155-based artificial miRNAs against heparanase (HPSE) constructed with BLOCK-iT™ Pol II miR RNAi Expression Vector Kit. The expression levels of HPSE declined significantly in both the mRNA and protein levels in HPSE-miRNA transfected melanoma cells that exhibited reduction of adhesion, migration, and invasion ability in vitro and in vivo. We also observed that HPSE miRNA could inhibit the expressions of chemokines of interleukin-8 (IL8) and chemokine (C-X-C motif) ligand 1 (CXCL1), at both the transcriptional and translational levels. Further study on its probable mechanism declared that down-regulation of IL8 and CXCL1 by HPSE-miRNA may be correlated with reduced growth-factor simulated mitogen-activated kinase (MAPK) phosphorylation including p38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) 1 and 2, which could be rescued by miRNA incompatible mutated HPSE cDNA. In conclusion, we demonstrated that artificial miRNAs against HPSE might serve as an alterative mean of therapy to low HPSE expression and to block the adhesion, invasion, and metastasis of melanoma cells. Furthermore, miRNA-based RNAi was also a powerful tool for gene function study.

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Insulin induces monocytic CXCL8 secretion by the mitogenic signalling pathway

Cited by 12 publications

References 24 publications

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

Neutrophil Paralysis in Plasmodium vivax Malaria

An Artificial miRNA against HPSE Suppresses Melanoma Invasion Properties, Correlating with a Down-Regulation of Chemokines and MAPK Phosphorylation

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