IL-4 enhances IEC-6 intestinal epithelial cell proliferation yet has no effect on IL-6 secretion

McGee, Dennis W.; Vitkus, S. J. D.

doi:10.1046/j.1365-2249.1996.d01-750.x

Cited by 17 publications

(7 citation statements)

References 14 publications

(21 reference statements)

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“…Serum IL‐4 levels were noticeably elevated in IL‐4R α −/− mice compared with WT animals, consistent with observations that IL‐4 production is an IL‐4Rα‐independent process in murine Leishmania infection 19. IL‐4 has been reported to have direct proliferative activity on intestinal epithelial cells 20. However, in the absence of IL‐4Rα chain function, no alternative signalling pathway for IL‐4 is currently recognized, so that increased serum IL‐4 levels are unlikely to contribute to AOM‐induced ACF development in our model.…”

Section: Discussionsupporting

confidence: 87%

Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Cuthbert

Orsi

et al. 2008

The Journal of Pathology

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Interleukin (IL)-4 receptor (IL-4R) alpha chain-dependent signalling by IL-4 and IL-13 promotes tumour growth and metastasis in mouse models of colorectal cancer. However, the role of IL-4R alpha-dependent signalling during the early, pre-malignant stages of colorectal carcinogenesis has not been investigated. Therefore, we investigated the effect of deletion of the IL-4R alpha gene on azoxymethane-induced colorectal aberrant crypt focus (ACF) multiplicity and size in Balb/c mice. IL-4R alpha(-/-) mice developed significantly more ACFs [median 8, inter-quartile range (IQR) 4-11.5; n = 9] than wild-type (WT) animals (median 4, IQR 1-6; n = 9; p = 0.04, Mann-Whitney U-test). There were significantly higher levels of IL-4 in serum from azoxymethane- and sham-treated IL-4R alpha(-/-) mice than WT animals, but no difference in serum IL-13 levels. In the absence of functional IL-4Rs, IL-13 can also signal via the IL-13R alpha2 receptor, leading to induction of transforming growth factor (TGF) beta, which has pro-tumourigenic activity at early stages of intestinal tumourigenesis. We found that mucosal TGFbeta mRNA levels and intestinal epithelial cell TGFbeta immunoreactivity were significantly higher in IL-4R alpha(-/-) mice than in WT animals. In summary, IL-4R alpha-dependent signalling has a protective, anti-neoplastic role during the post-initiation phase of azoxymethane-induced colorectal carcinogenesis in Balb/c mice. Our data should prompt thorough investigation of the role of IL-4R alpha-dependent signalling during human colorectal carcinogenesis, particularly as antagonism of IL-4R signalling represents a therapeutic strategy for asthma and other allergic diseases.

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Section: Discussionsupporting

confidence: 87%

Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Cuthbert

Orsi

et al. 2008

The Journal of Pathology

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“…IEC-6 cells [32] (ATCC) were seeded at 50,000 cells per well in corning 96 well flat bottomed micro titer plates and incubated overnight at a volume of 100 µl. 10 µl plant extracts ( W. ugandensis, W. somnifera, P. africana & P.barbatus ) at eight different concentrations each serially diluted were added and cells incubated for a further 72hours.…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial Activity and Probable Mechanisms of Action of Medicinal Plants of Kenya: Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus

et al. 2013

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Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus are used traditionally in Kenya for treatment of microbial infections and cancer. Information on their use is available, but scientific data on their bioactivity, safety and mechanisms of action is still scanty. A study was conducted on the effect of organic extracts of these plants on both bacterial and fungal strains, and their mechanisms of action. Extracts were evaluated through the disc diffusion assay. Bacteria and yeast test strains were cultured on Mueller-Hinton agar and on Sabouraud dextrose agar for the filamentous fungi. A 0.5 McFarland standard suspension was prepared. Sterile paper discs 6 mm in diameter impregnated with 10 µl of the test extract (100 mg/ml) were aseptically placed onto the surface of the inoculated media. Chloramphenicol (30 µg) and fluconazole (25 µg) were used as standards. Discs impregnated with dissolution medium were used as controls. Activity of the extracts was expressed according to zone of inhibition diameter. MIC was determined at 0.78–100 mg/ml. Safety studies were carried using Cell Counting Kit 8 cell proliferation assay protocol. To evaluate extracts mechanisms of action, IEC-6 cells and RT-PCR technique was employed in vitro to evaluate Interleukin 7 cytokine. Investigated plants extracts have both bactericidal and fungicidal activity. W. ugandensis is cytotoxic at IC50<50 µg/ml with MIC values of less than 0.78 mg/ml. Prunus africana shuts down expression of IL 7 mRNA at 50 µg/ml. W. somnifera has the best antimicrobial (1.5625 mg/ml), immunopotentiation (2 times IL 7 mRNA expression) and safety level (IC50>200 µg/ml). Fractions from W. ugandensis and W. somnifera too demonstrated antimicrobial activity. Mechanisms of action can largely be attributed to cytotoxicity, Gene silencing and immunopotentiation. Use of medicinal plants in traditional medicine has been justified and possible mechanisms of action demonstrated. Studies to isolate and characterize the bioactive constituents continue.

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“…Direct effects of interleukins on epithelial cells in vitro have been demonstrated by IL-4 (which is stimulatory) and IL-6 and IL-11 (which are inhibitory) (Booth & Potten 1995;Peterson et al 1996;McGee & Vitkus 1996). There is also increasing evidence for an interaction between the interleukins and conventional growth factors as a mechanism of controlling epithelial, and possibly stem cell, proliferation.…”

Section: Growth Factorsmentioning

confidence: 99%

The intestinal epithelial stem cell: the mucosal governor

Potten

Booth

Pritchard

1997

Int J Experimental Path

445

326

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Summary. All epithelial cells in the small and large intestine are thought to originate from stem cells located towards the base of the crypts of Lieberkü hn. To-date, there are no specific intestinal stem cell markers, hence stem cell properties can only be inferred. A range of experimental techniques have been employed including cell position mapping, radiation regeneration (clonogenic) assays, chimeric and transgenic mice. This review discusses the implications of experiments performed using these techniques in order to deduce the number, location and functional properties of stem cells. Stem cell homeostasis is maintained by cell proliferation and death 'through apoptosis'. The various growth and matrix factors and genes which may control these processes, and be important for stem cell function, are discussed along with their carcinogenic and clinical implications.Keywords: stem cell, intestine, apoptosis, epithelium Proliferative organization of the intestinal epitheliumThe lumenal surface of the intestine is lined by a simple columnar epithelium. The surface of both the small and large intestine is folded into a number of deep cavities or crypts of Lieberkü hn, which are embedded in connective tissue. In the small intestine the surface area is further increased by finger-like projections, or villi, also covered by epithelium, which protrude into the gut lumen. Although the crypts are approximately 10 × smaller than the villi, they are much more numerous (7 × more in the duodenum, 4 × more in the ileum, Wright & Alison 1984). The effect of these numerous 'pits and projections' is to form a huge surface area. This surface area is further expanded by the presence of a carpet-like covering of microvilli on the apical (lumenal) surface of the columnar epithelial cells.The functional cells of the epithelium are located predominantly towards the lumenal pole of the cryptvillus axis (i.e. on the villi of the small intestine and at the top of the crypts of the large intestine). Once they have fulfilled their differentiated function (brush border enzyme secretion, mucus secretion, nutrient and water absorption) the cells senesce and are sloughed off into the lumen itself, possibly after initiating some aspects of the Int.

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IL-4 enhances IEC-6 intestinal epithelial cell proliferation yet has no effect on IL-6 secretion

Cited by 17 publications

References 14 publications

Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Lack of interleukin‐4 receptor α chain‐dependent signalling promotes azoxymethane‐induced colorectal aberrant crypt focus formation in Balb/c mice

Antimicrobial Activity and Probable Mechanisms of Action of Medicinal Plants of Kenya: Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus

The intestinal epithelial stem cell: the mucosal governor

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