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. 2014:2014:136329.
doi: 10.1155/2014/136329. Epub 2014 Aug 18.

The possible role of the novel cytokines il-35 and il-37 in inflammatory bowel disease

Yanmei Li  1 , Yanan Wang  1 , Ying Liu  1 , Yatian Wang  1 , Xiuli Zuo  1 , Yanqing Li  1 , Xuefeng Lu  1
Affiliations

VSports在线直播 - The possible role of the novel cytokines il-35 and il-37 in inflammatory bowel disease

Yanmei Li et al. Mediators Inflamm. 2014.

Abstract (VSports)

Interleukin- (IL-) 35 and IL-37 are newly discovered immune-suppressing cytokines. They have been described in inflammatory diseases such as collagen-induced arthritis and asthma. However, their expressions in inflammatory bowel disease (IBD) patients have not been yet explored. Our aim was to evaluate serum and inflamed mucosal levels in IBD patients. In 20 ulcerative colitis (UC) patients, 7 Crohn's disease (CD) patients, and 15 healthy subjects, cytokine levels in serum were determined using ELISA and mucosal expression studies were performed by immunohistochemistry, quantitative real-time PCR, and Western blot. The results showed that serums IL-35 and IL-37 levels were significantly decreased in UC and CD patients compared with healthy subjects VSports手机版. The cytokines levels correlated inversely with UC activity. IL-35 was expressed in infiltrating immune cells while IL-37 in intestinal epithelial cells as well as inflammatory cells. IBD patients had significantly higher Ebi3, p35 (two subunits of IL-35), and IL-37b gene expressions; IL-35 and IL-37 protein expressions were higher in IBD patients compared with controls. The study showed that serums IL-35 and IL-37 might be potentially novel biomarkers for IBD. Intestinal IL-35 and IL-37 proteins are upregulated, suggesting that regulating the expression of the two cytokines may provide a new possible target for the treatment of IBD. .

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Figures

Figure 1
Figure 1
There was an intermediate inverse correlation between the Mayo score and serum IL-35 levels (a). IL-37 levels were moderately negatively correlated with Mayo score (b).
Figure 2
Figure 2
Photomicrographs of immunostaining for IL-35 in human colon from patients with UC (a and b), patients with CD (c and d), and healthy controls (e and f). No staining was found in the control group (e and f), and IL-35 was expressed in infiltrating immune cells (morphologically resembling lymphocytes) but not in epithelial cells. The staining was mostly cytoplasmic, and red arrows depicted immunoreactive positive cells. The number of IL-35-expressing cells in inflamed colonic tissue of patients with UC was higher than in CD patients' tissue. Original magnification: (a), (c), (e) ×200; (b), (d), (f) ×400.
Figure 3
Figure 3
Detection of Ebi3 and p35 mRNA by qRT-PCR. Ebi3 (a) and p35 (b) were significantly overexpressed in endoscopic specimens in both UC patients and CD patients as compared to controls (P < 0.001). Ebi3 and p35 mRNA expression in UC and CD biopsies did not reach statistical significance.
Figure 4
Figure 4
Detection of IL-35 in protein extracts of endoscopic specimens by Western blot. Representative Western blot of IL-35 and GAPDH (a) proteins levels in UC and CD patients and healthy controls. A significant upregulation of IL-35 was observed in inflamed mucosa of patients as compared to controls (P < 0.001) and IL-35 protein expression in UC biopsies was higher than that in CD biopsies (b).
Figure 5
Figure 5
Photomicrographs of immunostaining for IL-37 in patients with UC (a and b), patients with CD (c and d), and control subjects (e and f). IL-37 was expressed by both immune and epithelial cells (a–d), and normal tissue had IL-37 expression, though with relatively small amount (e and f). Besides strong cytoplasmic staining, few single lamina propria mononuclear cells showed nuclear expression of IL-37.
Figure 6
Figure 6
IL-37 gene expression in colonic mucosa from IBD patients. A significant increase in IL-37 mRNA was shown in inflamed mucosa of patients as compared to controls.
Figure 7
Figure 7
Detection of IL-37 in protein extracts of endoscopic specimens by Western blot. Representative Western blot of IL-37 and GAPDH (a) proteins levels in UC and CD patients and healthy controls. IL-37 protein expression was found to be higher in UC patients and CD patients compared to healthy subjects and the expression levels of IL-37 protein were higher in the samples of UC patients than that of CD samples (b).
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