Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease

Binion, DG; West, G. A.; Ina, Kenji; Ziats, NP; Sn, Emancipator; Fiocchi, Claudio

doi:10.1053/gast.1997.v112.pm9178682

Cited by 190 publications

(154 citation statements)

References 1 publication

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“…The use of human tissues was approved by the Institutional Review Board of the Medical College of Wisconsin. HIMEC were isolated as previously described (40). In brief, mucosal strips from resected normal colon were washed, minced, and digested in collagenase type II solution (Worthington, Lakewood, NJ; 2 mg/ml).…”

Section: Methodsmentioning

confidence: 99%

Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2

Heidemann¹,

Ogawa²,

Dwinell³

et al. 2003

Journal of Biological Chemistry

431

321

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Section: Methodsmentioning

confidence: 99%

Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2

Heidemann¹,

Ogawa²,

Dwinell³

et al. 2003

Journal of Biological Chemistry

431

321

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“…HIMEC samples were isolated as described previously (Binion et al, 1997;Heidemann et al, 2004). To isolate colonic crypts the muscularis externa was detached from surgical specimens and the resulting mucosal strips were washed, minced and incubated 90 min at room temperature in phosphate-buffered saline (PBS) containing 3 mM EDTA and 1 mM DTT and the tube was shaken to liberate crypts.…”

Section: Human Mucosal Samplesmentioning

confidence: 99%

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis

et al. 2006

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Cellular metastasis is the most detrimental step in carcinoma disease progression, yet the mechanisms that regulate this process are poorly understood. CXCL12 and its receptor CXCR4 are co-expressed in several tissues and cell types throughout the body and play essential roles in development. Disruption of either gene causes embryonic lethality due to similar defects. Post-natally, CXCL12 signaling has a wide range of effects on CXCR4-expressing cells, including the directed migration of leukocytes, lymphocytes and hematopoietic stem cells. Recently, this signaling axis has also been described as an important regulator of directed carcinoma cell metastasis. We show herein that while CXCR4 expression remains consistent, constitutive colonic epithelial expression of CXCL12 is silenced by DNA hypermethylation in primary colorectal carcinomas as well as colorectal carcinomaderived cell lines. Inhibition of DNA methyltransferase (Dnmt) enzymes with 5-aza-2 0 -deoxycytidine or genetic ablation of both Dnmt1 and Dnmt3b prevented promoter methylation and restored CXCL12 expression. Re-expression of functional, endogenous CXCL12 in colorectal carcinoma cells dramatically reduced metastatic tumor formation in mice, as well as foci formation in soft agar. Decreased metastasis was correlated with increased caspase activity in cells re-expressing CXCL12. These data constitute the unique observation that silencing CXCL12 within colonic carcinoma cells greatly enhances their metastatic potential.

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“…Endothelial activation by LPS leads to enhanced leukocyte adhesion and tissue recruitment from the circulation, a key regulatory step in the inflammatory response. We have reported that cultured human intestinal microvascular endothelial cells (HIMEC) are also strongly activated by bacterial LPS, as demonstrated by significantly enhanced CAM expression and increased leukocyte-binding activity (1). As described in monocytes and macrophages, endothelial cells are also believed to undergo activation through ligation of Toll-like receptor 4 (TLR4), a recently identified receptor and signal transducer of LPS (2)(3)(4).…”

mentioning

confidence: 99%

Mechanisms of Endotoxin Tolerance in Human Intestinal Microvascular Endothelial Cells

Ogawa¹,

Rafiee²,

Heidemann³

et al. 2003

The Journal of Immunology

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Lipopolysaccharide (endotoxin) tolerance is well described in monocytes and macrophages, but is less well characterized in endothelial cells. Because intestinal microvascular endothelial cells exhibit a strong immune response to LPS challenge and play a critical regulatory role in gut inflammation, we sought to characterize the activation response of these cells to repeated LPS exposure. Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were stimulated with LPS over 6–60 h and activation was assessed using U937 leukocyte adhesion, expression of E-selectin, ICAM-1, VCAM-1, IL-6, IL-8, manganese superoxide dismutase, HLA-DR, and CD86. Effect of repeat LPS stimulation on HIMEC NF-κB and mitogen-activated protein kinase (MAPK) activation, generation of superoxide anion, and Toll-like receptor 4 expression was characterized. LPS pretreatment of HIMEC for 24–48 h significantly decreased leukocyte adhesion after subsequent LPS stimulation. LPS pretreatment inhibited expression of E-selectin, VCAM-1, IL-6, and CD86, while ICAM-1, IL-8, and HLA-DR were not altered. Manganese superoxide dismutase expression increased with repeated LPS stimulation, with a reduction in intracellular superoxide. NF-κB activation was transiently inhibited by LPS pretreatment for 6 h, but not at later time points. In contrast, p44/42 MAPK, p38 MAPK, and c-Jun N-terminal kinase activation demonstrated inhibition by LPS pretreatment 24 or 48 h prior. Toll-like receptor 4 expression on HIMEC was not altered by LPS. HIMEC exhibit endotoxin tolerance after repeat LPS exposure in vitro, characterized by diminished activation and intracellular superoxide anion concentration, and reduced leukocyte adhesion. HIMEC possess specific mechanisms of immunoregulatory hyporesponsiveness to repeated LPS exposure.

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Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease

Cited by 190 publications

References 1 publication

Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2

Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis

Mechanisms of Endotoxin Tolerance in Human Intestinal Microvascular Endothelial Cells

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