Mast cell changes in experimental diabetes: focus on attenuation of allergic events

Carvalho, Vinícius Frias; Barreto, Emiliano; Cordeiro, Renato S.B.; Lagente, Vincent; Martins, Marco A.; Silva, Patrı́cia M.R. e

doi:10.1590/s0074-02762005000900021

Cited by 6 publications

(5 citation statements)

References 62 publications

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“…It has been reported that alloxan-treated rats have a selective reduction in the number of pleural mast cells, a phenomenon also observed after treatment with the alternative diabetogenic agent streptozotocin (Diaz et al 1996). Additionally, we have also demonstrated that diabetic sensitized animals are clearly resistant to local and systemic allergic inflammatory responses (Carvalho et al 2005). In the case of systemic anaphylaxis, a substantial reduction in the lethality, intestinal haemorrhage and refractoriness of small intestine to antigen stimulation in vitro has been described, suggesting that mast cell depletion in the intestinal tissue might play a role in the refractoriness of diabetic rats to anaphylactic shock .…”

supporting

confidence: 73%

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Reduced expression of IL‐3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones

Carvalho

Barreto

Farias-Filho

et al. 2009

Int J Experimental Path

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Rats turned diabetic by alloxan treatment are refractory to systemic anaphylactic shock, in a direct association with reduced intestinal haemorrhage and tissue response to antigen challenge. As diabetic rats show reduction in mast cell numbers in different body compartments, this study was undertaken to investigate the influence of alloxan diabetes on mast cell population as well as the expression of the mast cell growth factor interleukin (IL)-3 in the small intestine of rats. We also analysed the putative involvement of endogenous insulin and glucocorticoid hormones in this phenomenon. There was a significant decrease in the number of mast cells present in the small intestine (ileum segment) of diabetic rats. Likewise, the immunohistochemical analysis revealed that IL-3 labelling was markedly attenuated in diabetic rats, as compared with normal animals, a phenomenon which paralleled with a decreased mRNA expression as attested by Reverse transcriptase-polymerase chain reaction technique. Treatment with insulin and with the steroid receptor antagonist RU 486 restored basal mast cell numbers, normal levels of IL-3 labelling and mRNA expression for IL-3 in the ileum of diabetic rats. In conclusion, our findings show that there is a causative relationship between down-regulation of mast cell numbers and the expression of IL-3 associated with diabetic state. In addition, as both parameters were suppressed by administration of insulin and RU 486, it indicates that an imbalance between the systemic levels of insulin and glucocorticoid hormones seems to be implicated in the reduction in intestinal mast cell population and refractoriness to antigen provocation in alloxan diabetes.

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supporting

confidence: 73%

“…1996). Additionally, we have also demonstrated that diabetic sensitized animals are clearly resistant to local and systemic allergic inflammatory responses (Carvalho et al. 2005).…”

mentioning

confidence: 85%

Reduced expression of IL‐3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones

Carvalho

Barreto

Farias-Filho

et al. 2009

Int J Experimental Path

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“…Data from epidemiological studies indicate an inverse relationship between atopic disorders such as asthma and type I diabetes mellitus [11][12][13]. It has been hypothesized that this is due to an imbalance of Th1/Th2 cytokine secretion [32].…”

Section: Discussionmentioning

confidence: 99%

“…Receptors of the insulin (Ins) receptor (IR) family are known to strongly activate the PI3K pathway by means of tyrosine phosphorylation of the Ins receptor substrate proteins, IRS1 and 2 [10]. Interestingly, data from recent and previous epidemiological studies in children with type I diabetes mellitus indicate an inverse relationship between atopic disorders (asthma, eczema, and hay fever) and diabetes mellitus [11][12][13]. In keeping with this, diabetic rats have been reported to exhibit markedly reduced inflammatory responses to allergen challenge in the airways and the pleural space, which can be reversed by treatment of the animals with Ins [14,15].…”

mentioning

confidence: 99%

Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway

Lessmann

Grochowy

Weingarten

et al. 2006

Experimental Hematology

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“…In vivo data suggest that metabolic status alters the outcome of mast cellderived inflammation. Rats with streptozoicin-or alloxan-induced type I diabetes exhibit severely compromised anaphylactic responses to antigen or secretagogue, as well as diminished airway sensitivity [7][8][9][10]. Indeed, reconstitution of mast cell responses reverses the refractoriness to allergen challenge that is seen in alloxan-induced diabetic rats [10,11].…”

Section: Introductionmentioning

confidence: 99%

Insulin-containing lipogenic stimuli suppress mast cell degranulation potential and up-regulate lipid body biogenesis and eicosanoid secretion in a PPARγ-independent manner

Greineisen

Shimoda

Maaetoft-Udsen

et al. 2012

Journal of Leukocyte Biology

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Lipid bodies are most studied in adipocytes, where the lipogenic action of insulin initiates their formation. Here, we test the hypothesis that insulin may regulate lipid body content in mast cells and hence, modify their proinflammatory potential. Our data show that insulin causes lipid body accumulation in RBL2H3 and BMMCs. Lipid body accumulation in mast cells is associated with enhanced levels of leukotriene-synthesizing enzymes (LTC4S and 5-LO). Increased basal and antigen-stimulated release of LTC4 is observed in insulin-treated mast cells. Concomitantly, the insulin-containing lipogenic stimulus induces a phenotypic change in mast cells, where this enhancement in leukotriene levels is accompanied by a marked down-regulation in secretory granule content and release in response to stimulus. Mast cells exposed to insulin exhibit altered scatter and fluorescence properties, accumulating in a SSC(lo)FSC(hi) population that exhibits decreased BS staining and degranulation responses and is enriched in NR-positive lipid bodies and eicosanoid synthesis enzymes. Lipid body accumulation in mast cells is mechanistically distinct from the process in adipocytes; for example, it is independent of PPARγ up-regulation and does not involve significant accumulation of conjugated glycerides. Thus, chronic exposure to metabolic stimuli, such as insulin, may be a determinant of the proinflammatory potential of the mast cell.

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Mast cell changes in experimental diabetes: focus on attenuation of allergic events

Cited by 6 publications

References 62 publications

Reduced expression of IL‐3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones

Reduced expression of IL‐3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones

Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway

Insulin-containing lipogenic stimuli suppress mast cell degranulation potential and up-regulate lipid body biogenesis and eicosanoid secretion in a PPARγ-independent manner

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