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. 2013;6(2):98-104.
Epub 2013 Jan 26.

Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in intestinal and mesenteric fat tissue of Crohn's disease

Raquel F Leal  1 , Marciane Milanski, Maria de Lourdes S Ayrizono, Andressa Coope, Viviane S Rodrigues, Mariana Portovedo, Luiza M F Oliveira, João J Fagundes, Cláudio S R Coy, Lício A Velloso
Affiliations

Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in intestinal and mesenteric fat tissue of Crohn's disease

Raquel F Leal et al. Int J Clin Exp Med. 2013.

Abstract

Introduction: Crohn's disease (CD) is a chronic intestinal ailment with a multifactorial etiology, whose incidence has increased during the last three decades. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected nearby the affected intestinal area; however, there are few studies on this aspect.

Aim: To evaluate inflammatory activity in intestinal mucosa and mesenteric fat tissue of patients with CD and controls.

Materials and methods: Ten patients with ileocecal CD and 16 patients with non-inflammatory disease (control groups) were studied. The specimens were snap-frozen and the expression of TLR-4, F4/80, IL1-β and IL-6 were determined by immunoblot of protein extracts. TLR4 RNA level were measured using RT-PCR. The t Test was applied (p<0.05). The local ethical committee approved the study.

Results: The intestinal mucosa of CD group had significantly higher protein levels of TLR-4, F4/80, IL-1β and IL-6 than the controls. The gene expression of TLR4 was lower in the intestinal mucosa of CD compared to the control group. Regard the mesenteric fat tissue, there was no statistical difference related to TLR-4, F4/80, IL-1β and IL-6 proteins expression.

Conclusions: These findings may result from an up-regulation of macrophage activation and intracellular pathways activated by bacterial antigens, which are more important in intestinal mucosa than fat tissue in CD patients. This may represent an anomalous regulation of innate immunity and could contribute to the production of proinflammatory mediators and disease development.

Keywords: Crohn’s disease; cytokines; inflammatory bowel disease; innate immunity.

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Figures

Figure 1
Figure 1
Surgical aspects of creeping fat in ileum with Crohn’s disease.
Figure 2
Figure 2
Representative Western blot analyses and determination (mean and standard deviation) of F4/80 and TLR4 proteins expressions in fat tissue of the control (FC) and Crohn’s disease (FCD) groups, and in intestinal tissue of the control (IC) and Crohn’s disease (ICD) groups. For illustration purpose each line band represents one patient. For all conditions, n=10, *p<0.05 vs Control.
Figure 3
Figure 3
Representative Western blot analyses and determination (mean and standard deviation) of IL-1β and IL-6 proteins expressions in fat tissue of the control (FC) and Crohn’s disease (FCD) groups, and in intestinal tissue of the control (IC) and Crohn’s disease (ICD) groups. For illustration purpose each line band represents one patient. For all conditions, n=10, *p<0.05 vs Control.
Figure 4
Figure 4
Results of TLR4 gene expression, determined by RT-PCR. For FCD Group, n=10; for FC Group, n=8, *p<0.05 vs control.
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