TY - JOUR

T1 - IL-33 is upregulated in colonocytes of ulcerative colitis

AU - Seidelin, Jakob Benedict

AU - Bjerrum, Jacob Tveiten

AU - Coskun, Mehmet

AU - Widjaya, Budiman

AU - Vainer, Ben

AU - Nielsen, Ole Haagen

AU - Seidelin, J.B.

AU - Bjerrum, J.T.

AU - Coskun, Mehmet

AU - Widjaya, Budiman

AU - Vainer, B.

AU - Nielsen, O.H.

PY - 2010

Y1 - 2010

N2 - Interleukin-33 (IL-33) is a novel member of the IL-1 cytokine family. It has been shown to elicit a Th2-like cytokine response in immunocompetent cells through binding and activation of the T1/ST2 receptor. IL-33 has recently been associated with immune responses to helminthic intestinal infections, airway inflammation and arthritis in animal models. We now report IL-33 to be produced by colonic epithelial cells in humans and it is highly upregulated in ulcerative colitis (UC). Little mRNA expression was found in control subjects (N=9), whereas patients with UC in remission (N=7) and active UC (N=9) had a 3-fold (p<0.006) and 13-fold (p<0.0002) increased expression, respectively. On the protein level, IL-33 in its uncleaved form was overexpressed in active UC compared to controls (p<0.006) and inactive UC (p<0.03). Immunohistochemistry of IL-33 confirmed expression in active UC in colonic epithelial cells, whereas no detectable epithelial expression was seen in control specimens. Caspase 1, which is known to activate IL-33, was expressed in colonocytes, albeit at just detectable levels when the activated p20 caspase 1 was measured. Since IL-33 recently has been shown to be biologically active in its pro-form, and cleavage seems to inactivate IL-33, IL-33 is suggested to be active in UC. We found no IL-33 expression in Caco2 cells, regardless of stimulation by pro-inflammatory cytokines. In contrast to the IL-33 expression data, we could not show any difference in the production of another member of the IL-1 cytokine family, IL-1beta. This is the first study to describe that IL-33 is upregulated in UC. If IL-33 is driving a Th2-like cytokine response in UC, inhibition of the IL-33 T1/ST2 receptor pathway could be a future therapeutic option in UC.

AB - Interleukin-33 (IL-33) is a novel member of the IL-1 cytokine family. It has been shown to elicit a Th2-like cytokine response in immunocompetent cells through binding and activation of the T1/ST2 receptor. IL-33 has recently been associated with immune responses to helminthic intestinal infections, airway inflammation and arthritis in animal models. We now report IL-33 to be produced by colonic epithelial cells in humans and it is highly upregulated in ulcerative colitis (UC). Little mRNA expression was found in control subjects (N=9), whereas patients with UC in remission (N=7) and active UC (N=9) had a 3-fold (p<0.006) and 13-fold (p<0.0002) increased expression, respectively. On the protein level, IL-33 in its uncleaved form was overexpressed in active UC compared to controls (p<0.006) and inactive UC (p<0.03). Immunohistochemistry of IL-33 confirmed expression in active UC in colonic epithelial cells, whereas no detectable epithelial expression was seen in control specimens. Caspase 1, which is known to activate IL-33, was expressed in colonocytes, albeit at just detectable levels when the activated p20 caspase 1 was measured. Since IL-33 recently has been shown to be biologically active in its pro-form, and cleavage seems to inactivate IL-33, IL-33 is suggested to be active in UC. We found no IL-33 expression in Caco2 cells, regardless of stimulation by pro-inflammatory cytokines. In contrast to the IL-33 expression data, we could not show any difference in the production of another member of the IL-1 cytokine family, IL-1beta. This is the first study to describe that IL-33 is upregulated in UC. If IL-33 is driving a Th2-like cytokine response in UC, inhibition of the IL-33 T1/ST2 receptor pathway could be a future therapeutic option in UC.

U2 - 10.1016/j.imlet.2009.11.001

DO - 10.1016/j.imlet.2009.11.001

M3 - Journal article

C2 - 19913053

VL - 128

SP - 80

EP - 85

JO - Immunology Letters

JF - Immunology Letters

SN - 0165-2478

IS - 1

ER -