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

Abstract

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.

Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice

“…Secondary antibodies conjugated with horseradish peroxidase (HRP) were all obtained from R&D Systems (Minneapolis, USA). To determine the specificity of staining, no primary antibody was used followed by incubation of section with secondary antibodies and detection reagents (18).…”

Different Roles of Mast Cells in Obesity and Diabetes: Lessons from Experimental Animals and Humans

“…Glucocorticoids exhibit anti-inflammatory activity by inhibiting tissue cytokine and SCF expression (Schleimer, 1993 ; Finotto et al, 1997 ), therefore participating in MC depletion in the intestines and other organs in diabetic rats (Pipkorn et al, 1989 ; Goldsmith et al, 1990 ; Finotto et al, 1997 ). Treatment with steroid receptor agonist RU486 (Carvalho Vde et al, 2009 ) or surgical bilateral adrenalectomy (Diaz et al, 2001 ) increases intestinal MC numbers and IL3 staining and IgE formation in diabetic mice – suggesting a negative correlation between MC–IgE system and serum glucocorticoid levels. Glucocorticoids also inhibit insulin secretion effectively through pancreatic β cells (Ludvik et al, 1993 ), and insulin treatment in alloxanated rats impairs the increase of systemic corticosterone.…”

Insights into the Characteristics and Functions of Mast Cells in the Gut

“…And reduced MC responses to bacterial antigen stimulation in C57BL/6 mice were confirmed in recent studies [63]. Diabetic mice showed reduced IL-3 and MC number levels, which could be induced by insulin, are associated with decreased immunity [64]. Other mediators, such as IL-4, stem cell factor, and nerve growth factor, have proven to suppress MC apoptosis in the human intestine in times of infection [65].…”