Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis

Kobori, Ayako; Yagi, Yuki; Imaeda, Hirotsugu; Ban, Hiromitsu; Bamba, Shigeki; Tsujikawa, Tomoyuki; Saito, Yasuharu; Fujiyama, Yoshihide; Andoh, Akira

doi:10.1007/s00535-010-0245-1

Cited by 219 publications

(194 citation statements)

References 31 publications

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“…In the investigation of IL-33 in colonic diseases, it has been found that the increase of IL-33 is related to the development of colorectal chronic inflammation (ulcerative colitis) (29,30), whereas the epidemiological studies from different countries have revealed that ulcerative colitis may significantly raise the CRC risk (33)(34)(35)(36)(37)(38)(39). Our current study, in our best knowledge, is the first study to demonstrate a dynamic change of IL-33 from the colorectal adenomas to the sporadic CRCs.…”

Section: Discussionmentioning

confidence: 56%

“…In human HCC, no significant difference in IL-33 serum levels was found in HCC compared to liver cirrhosis and healthy controls (28). The role of IL-33 in inflammatory bowel diseases has been studied, extensive evidence now suggests that IL-33 is activated in the inflamed mucosa of ulcerative colitis and plays a critical role in the development of chronic inflammation (29,30), which is a risk factor for CRC. However, information is still very limited regarding the IL-33/ST2 axis in sporadic colorectal tumor-bearing hosts, particularly regarding the changes in the colorectal adenoma-carcinoma sequence.…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

Cui

Gundersen

et al. 2014

Cancer Immunol Immunother

108

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Most sporadic colorectal cancers (CRCs) develop from preexisting adenomas. The transition from an adenoma to a CRC leads to disruption in cytokine secretion and immune imbalance.Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family, and involved in the regulation of immune function and development of chronic colorectal inflammation and cancers. However, the activation of the IL33/ST2 axis alongside the colorectal adenoma-carcinoma sequence is poorly understood. Our aim is to evaluate the dynamics between the IL-33/ST2 axis and the human colorectal normaladenoma -carcinoma sequence. The expression of IL-33 in adenomas (n=50) determined by real-time PCR was significantly higher than that in the colorectal mucosa from normal individuals. The expression of IL-33 was also increased in CRCs (n=50) when compared to the normal control group. Significantly lower levels of IL-33 where found in the CRCs compared with the adenomas; moreover, the analysis revealed that a high IL-33 level was associated with a low dysplasia degree in the adenomas, as well as with a statistically nonsignificant increase of survival time in the CRC patients. The increased expression of IL-33 in adenomas/CRCs was confirmed by immunohistochemistry (IHC) which showed that IL-33 immunoreactivity was expressed in the adenomatous/cancerous epithelium, whereas it was undetectable in the normal controls. IHC also confirmed that the IL-33 receptor (ST2) is increased in tumor stromal cells. Double IHCs identified that IL-33 immunoreactivity was in the tumor stromal myofibroblasts and microvessels. In conclusion, the expression of IL-33 in the tumor microenvironment was dynamically altered along the colorectal adenomacarcinoma sequence; and may be a potential predictor for the progression of the adenoma to the CRC.3

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

Cui

Gundersen

et al. 2014

Cancer Immunol Immunother

108

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“…IL-33 expression was significantly elevated in active lesions from patients with UC, but was not detected in inactive lesions in UC patients or in lesions from patients with either active or inactive Crohn's disease. IL-33 is specifically enhanced in inflamed mucosa of UC, and may play an important role in the pathophysiology of UC (33).…”

Section: Discussionmentioning

confidence: 99%

CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation

Xu¹,

Dong

et al. 2016

Ann. Transl. Med.

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Background: Ulcerative colitis (UC) is a nonspecific inflammatory disease for which medications and therapeutic strategies have only been moderately successful. CBLB502, a toll-like receptor 5 (TLR5) agonist derived from Salmonella flagellin, exhibits anticancer and radioprotective activities via modulation of TLRs and the nuclear factor kappa B (NF-κB) signaling pathway and can protect against acute renal ischemic failure. In this study, we intend to examine the effects of CBLB502 on both TLR responses and the interleukin (IL) and NF-κB signaling pathways in UC treatment.Methods: The UC mouse model was prepared in BALB/c mice by administering 2,4,6-trinitrobenzene sulfonic acid (TNBS). CBLB502 was used as the therapeutic drug. After CBLB502 therapy, the IL and tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Total RNA and protein of colon samples was extracted.Results: We found that CBLB502 had a distinctive therapeutic effect in the UC model. In control group animals, IL-10 expression in serum was 91.48±24.38 ng/mL; this was higher than in the model group (59.36±14.46 ng/mL, P<0.05) or the treatment group (54.29±5.83 ng/mL, P<0.05). In model group animals, the concentration of TNF-α in serum was 140.11±12.70 ng/mL, which was lower than protein levels in the control group (173.86±29.26 ng/mL, P<0.05). The mRNA levels of TLR1,2,3,4,6,7,8, and 9 in the CBLB502 treatment group were significantly lower than in the model group (P<0.05). Western blot revealed that CBLB502 also reduced NF-κB expression in the mouse colon, but that NF-κB expression was not significantly lower than the model group.Conclusions: CBLB502 can reduce mucosal damage induced by TNBS and inhibit inflammation and TLR expression. The inhibition of UC by CBLB502 is strictly TLR-IL-dependent and is dose-dependent within the efficacious dose range. Therefore, our results suggested that CBLB502 might be a candidate drug for the treatment of UC.

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“…Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and relapsing intestinal disorders of unknown etiology (1)(2)(3)(4)(5). There is currently no pharmaceutical cure for IBD, and hence treatment options aim for inducing and maintaining remission.…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus (FK506) suppresses TNF-α-induced CCL2 (MCP-1) and CXCL10 (IP-10) expression via the inhibition of p38 MAP kinase activation in human colonic myofibroblasts

Aomatsu

Imaeda

Takahashi

et al. 2012

International Journal of Molecular Medicine

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Abstract. In order to investigate the molecular mechanisms underlying the immunosuppressive effects of tacrolimus (FK506) on intestinal inflammation, we examined whether FK506 effects cytokine/chemokine secretion in human colonic myofibroblasts. Human colonic myofibroblasts were isolated from normal human colonic tissue. The mRNA and protein expression for human CCL2 and CXCL10 were analyzed by real-time PCR and ELISA, respectively. p38 MAP kinase activation was evaluated by western blotting. Tacrolimus (1 µM) suppressed tumor necrosis factor (TNF)-α-induced CCL2 and CXCL10 mRNA expression, but did not modulate TNF-α-induced interleukin (IL)-6 or CXCL8 mRNA expression. Dose-dependent, inhibitory effects of tacrolimus on CCL2 and CXCL10 expression were observed at the mRNA and protein levels. Significant inhibitory effects of tacrolimus were observed at concentrations as low as 0.5 µM for CCL2 and 0.1 µM for CXCL10, respectively. TNF-α-induced CCL2 and CXCL10 expression depended on p38 MAP kinase activation, and tacrolimus strongly inhibited the TNF-α-induced phosphorylation of p38 MAP kinase. Tacrolimus did not affect interferon (IFN)-γ-induced signaling transducer and activator of transcription (STAT)-1 phosphorylation, nor did it modulate CXCL10 mRNA and protein expression. In conclusion, tacrolimus suppressed CCL2 and CXCL10 expression in human colonic myofibroblasts. These inhibitory effects of tacrolimus may play key roles in the therapeutic effects of colonic inflammation in inflammatory bowel disease (IBD) patients.

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Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis

Abstract: IL-33, derived from colonic SEMFs, may play an important role in the pathophysiology of UC.

Cited by 219 publications

References 31 publications

Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation

Tacrolimus (FK506) suppresses TNF-α-induced CCL2 (MCP-1) and CXCL10 (IP-10) expression via the inhibition of p38 MAP kinase activation in human colonic myofibroblasts

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