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 - 2010/1/18
Y1 - 2010/1/18
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-1β. 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-1β. 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
SN - 0165-2478
VL - 128
SP - 80
EP - 85
JO - Immunology Letters
JF - Immunology Letters
IS - 1
ER -