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Sökning: onr:"swepub:oai:DiVA.org:oru-25590" > Interplay between T...

Interplay between Th1 and Th17 effector T cell pathways in the pathogenesis of spontaneous colitis and colon cancer in the Gai2-deficient mouse

Gotlind, Yu-Yuan (författare)
Fredin, Maria Fritsch (författare)
Kumawat, Ashok Kumar (författare)
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Strid, Hilja (författare)
Willen, Roger, (författare)
Uppsala universitet, Institutionen för immunologi, genetik och patologi
Rangel, Ignacio (författare)
Bland, Paul W. (författare)
Hornquist, Elisabeth Hultgren (författare)
Götlind, Y. Y., (författare)
Department of Microbiology and Immunology, Institute of Biomedicine and MIVAC, Sahlgrenska Academy, Göteborg, Sweden
Fritsch Fredin, M., (författare)
Department of Bioscience, AstraZeneca, Mölndal, Sweden
Willén, R., (författare)
Department of Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden
Hultgren Hörnquist, Elisabeth, 1965- (författare)
Örebro universitet, Institutionen för läkarutbildning, Department of Clinical Medicine
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för immunologi, genetik och patologi. (creator_code:org_t)
Örebro universitet Institutionen för hälsovetenskap och medicin. (creator_code:org_t)
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Örebro universitet Institutionen för läkarutbildning. (creator_code:org_t)
Göteborgs universitet Sahlgrenska akademin. Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi. 
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2013
Engelska.
Ingår i: International Immunology. - Oxford, United Kingdom : Oxford University Press. - 0953-8178. ; 25:1, s. 35-44
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Gαi2-deficient mice spontaneously develop colitis. Using xMAP technology and RT-PCR, we investigated cytokine/chemokine profiles during histologically defined phases of disease: (i) no/mild, (ii) moderate, (iii) severe colitis without dysplasia/cancer and (iv) severe colitis with dysplasia/cancer, compared with age-matched wild-type (WT) littermates. Colonic dysplasia was observed in 4/11 mice and cancer in 1/11 mice with severe colitis. The histology correlated with progressive increases in colon weight/cm and spleen weight, and decreased thymus weight, all more advanced in mice with dysplasia/cancer. IL-1β, IL-6, IL-12p40, IL-17, TNF-α, CCL2 and CXCL1 protein levels in colons, but not small intestines increased with colitis progression and were significantly increased in mice with moderate and severe colitis compared with WT mice, irrespective of the absence/presence of dysplasia/cancer. CCL5 did not change during colitis progression. Colonic IL-17 transcription increased 40- to 70-fold in all stages of colitis, whereas IFN-γ mRNA was gradually up-regulated 12- to 55-fold with colitis progression, and further to 62-fold in mice with dysplasia/cancer. IL-27 mRNA increased 4- to 15-fold during the course of colitis, and colonic IL-21 transcription increased 3-fold in mice with severe colitis, both irrespective of the absence/presence of dysplasia/cancer. FoxP3 transcription was significantly enhanced (3.5-fold) in mice with moderate and severe colitis, but not in mice with dysplasia/cancer, compared with WT mice. Constrained correspondence analysis demonstrated an association between increased protein levels of TNF-α, CCL2, IL-1β, IL-6 and CXCL1 and dysplasia/cancer. In conclusion, colonic responses are dominated by a mixed T(h)1/T(h)17 phenotype, with increasing T(h)1 cytokine transcription with progression of colitis in Gαi2(-/-) mice.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)
MEDICAL AND HEALTH SCIENCES  (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

chemokines
constrained correspondence analysis
dysplasia
inflammatory bowel disease
real-time RTPCR
Medicine
Medicin
Chemokines
real-time RT–PCR

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