Reduced expression of microenvironmental Th1 cytokines accompanies adenomas-carcinomas sequence of colorectum.
Cytokines have been suggested to be key factors in modulating immune response against tumorigenesis in the microenvironment. Therefore, characterization of cytokine expression along the colorectal adenoma-carcinoma sequence may add important information for understanding the immune-related mechanisms of the development of colorectal carcinoma (CRC). In this study, biopsies from 32 patients with colorectal adenoma (CRA), 20 patients with CRC and 18 healthy controls were examined. Cytokine gene expressions of interleukin-4 (IL-4), IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and its upstream inducers (IL-12A and IL-18) were measured at messenger RNA (mRNA) level with quantitative real-time PCR (Q-PCR). Cytokine expressing cells were characterized using immunohistochemistry (IHC). A distinct different cytokine profile between adenoma and CRC was observed: the Th1 cytokines (IFN-gamma, TNF-alpha, IL-12A and IL-18) were increased in local tissues of CRA and decreased in CRC. Consistent with the quantitative cytokine data, IHC examinations revealed slightly increased densities of Th1 cytokine-expressing cells in CRA and a remarkably decreased density of the Th1 cells in CRC. In CRA, the cytokine-expressing cells were highly polarized to the subepithelial stroma while the cells were evenly distributed through the stroma in CRC. In conclusion, distinct changes in the Th1 cytokine profile appear along the colorectal adenoma-carcinoma sequence. This may reflect a change in the host immune regulatory function in the adenoma-carcinoma sequence.
Cui
Guanglin
G
Laboratory of Gastroenterology, Institute of Clinical Medicine, Faculty of Medicine, University of Tromsø, 9037 Tromsø, Norway. guanglin.cui@fagmed.uit.no
Goll
Rasmus
R
Olsen
Trine
T
Steigen
Sonja Eriksson
SE
Husebekk
Anne
A
Vonen
Barthold
B
Florholmen
Jon
J
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers