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Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells

, : Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells. Journal of Immunology 170(12): 5956-5964

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-kappaB 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-kappaB 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.


PMID: 12794122

DOI: 10.4049/jimmunol.170.12.5956

Other references

Chester, A.H.; Yacoub, M., 1990: Vascular reactivity and endothelial function of bypass grafts. Current Opinion in Cardiology 5(6): 733-736

Kistner, A.; Lhommée, Eénie.; Krack, P., 2014: Mechanisms of body weight fluctuations in Parkinson's disease. Typical body weight changes are known to occur in Parkinson's disease (PD). Weight loss has been reported in early stages as well as in advanced disease and malnutrition may worsen the clinical state of the patient. On the other hand, an incr...

Forsyth, R.; Bartlett, K.; Burchell, A.; Eyre, J.A., 1994: Availability of astrocyte glycogen to neurons as glucose at times of neuronal need The astrocyte-neuron functional unit. Clinical Science (London) 87(1): 36P-37P

Anonymous, 2011: Vasculitis in Sjogren’s Syndrome. Sj gren s syndrome is a chronic autoimmune disease that is commonly manifested by immune attack on the exocrine glands with resultant dry eyes and dry mouth. Sj gren s syndrome patients also have disease in other organs. One of the most common ext...

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Ishii, M.; Seekkuarachchi, H.; Tamura, H.; Tang, Z., 2004: 3D flash lag illusion. Objective of this research is to study the presence of 3D flash lag illusion created by a moving object that has a motion-in-depth and a flash object. An object consisting of two thin sticks was simulated to approach the subject who observed it wi...

Torres, J.; Romero, H., 2012: In vitro antifungal activity of ajoene on five clinical isolates of Histoplasma capsulatum var. capsulatum. The number of histoplasmosis cases have considerably increased since the advent of AIDS, and the therapy for this mycosis is not always effective, as well as having adverse effects. To evaluate the inhibitory effect of ajoene on five clinical isol...

Heiner, M.; Hui, J.; Schreiner, S.; Hung, L-Hsueh.; Bindereif, A., 2010: HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition. Heterogeneous nuclear ribonucleoprotein (hnRNP) L can regulate alternative mRNA splicing in diverse ways, binding to exonic or intronic sites and acting as either an activator or repressor. To investigate the mechanistic basis of hnRNP L-regulated...

Sander, I., 1964: On The Problem Of The Genesis Of Gm-Antibodies. Blut 10: 32-32

Hasegawa H.S., 1988: Seismogenesis in Eastern Canada. Seismological Research Letters 59(4): 219-225