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Biomedical subjects

C van Kooten

Publications and source records attributed to C van Kooten.

67 records · Page 4Linked to original sources

The action of interleukin 6 on lymphoid populations.

We have analysed the role of IL-6 in activation of human lymphocytes isolated from peripheral blood. We found little effect of IL-6 on proliferation of T cells. IL-6 did stimulate production of IgM by B cells. However, it did not behave as a terminal differentiation factor and was required only during the first two days of the culture. Under most conventional stimulation conditions T cells themselves produce little or no IL-6. High IL-6 production could be induced by stimulating the cells with a combination of phorbol-12-myristate 13-acetate (PMA) and anti-CD28 antibodies.

B-Lymphocytes↗

Monokine production by human T cells; IL-1 alpha production restricted to memory T cells.

The production of cytokines is a key event of inflammation. In this report we demonstrate that normal human T cells are capable to produce IL-1 alpha, IL-6, and TNF-alpha, cytokines formerly considered to be monokines. This production was optimal after stimulation with a combination of anti-CD2, PMA, and anti-CD28. All three cytokines were produced in a bioactive form. Both naive (CD4+CD45RA+) and memory (CD4+CD45RO+) subsets of T cells were shown to produce similar amounts of IL-6 and TNF-alpha. In contrast the production of IL-1 alpha was found to be completely restricted to the CD4+CD45RO+ subset. The finding that T cells are such potent producers of these important mediators of the inflammatory response might be a key observation in the appreciation of the role of T cells in chronic inflammation.

CD4 Antigens↗

Effects of anti-inflammatory agents on mucosal inflammation induced by infection with gram-negative bacteria.

Gram-negative bacterial infections of the urinary tract elicit a mucosal inflammatory response. Interleukin-6 is secreted into the urine, and polymorphonuclear leukocytes (PMNL) are recruited. In the present study we examined the effect of anti-inflammatory agents on these parameters and on bacterial clearance from the kidneys. Dexamethasone reduced interleukin-6 secretion, the PMNL response, and bacterial clearance. Diclofenac abolished the urinary interleukin-6 response but reduced the PMNL response and bacterial clearance only at the highest concentrations. Indomethacin drastically decreased bacterial clearance without the corresponding effect on interleukin-6 production or the PMNL response. The results demonstrate that the inhibition of inflammation impairs bacterial clearance from the kidneys. This is, however, not a direct function of inhibited interleukin-6 production or PMNL recruitment.

Animals↗

Interleukin-6 induced at mucosal surfaces by gram-negative bacterial infection.

Interleukin-6 (IL-6) was produced in response to mucosal and systemic infection of mice with gram-negative bacteria. The IL-6 response was controlled by the lipopolysaccharide gene, Lps; in C3H/HeN mice (Lpsn/Lpsn), the urinary IL-6 levels increased within 30 min after challenge with Escherichia coli, but no response occurred in C3H/HeJ mice (Lpsd/Lpsd). In lipopolysaccharide-responder mice, the levels of local and systemic IL-6 were related to the degree of infection. The urinary response dominated after intravesical challenge, and the serum response dominated after intraperitoneal challenge. The results demonstrate that IL-6 is activated as part of lipopolysaccharide-induced mucosal and systemic responses to gram-negative bacterial infections.

Animals↗

The first derivative as a means of synchronizing pulsatile flow velocity and vessel diameter waveforms in the fetal descending aorta.

In order to calculate volume flow, blood flow velocity and pulsatile vessel diameter waveforms in the lower thoracic part of the descending aorta of the fetal lamb and human fetus were matched for identical cardiac cycle length by fetal ECG and the first derivative of these waveforms. Volume flow values were not essentially different using either method. There is simultaneous onset of the blood flow velocity and pulsatile vessel diameter waveforms. The first derivative can reliably replace the fetal ECG as a means of synchronizing blood flow velocity and pulsatile vessel diameter waveforms in the fetal descending aorta.

Animals↗

Blood flow velocity waveforms in the descending fetal aorta: comparison between normal and growth-retarded pregnancies.

A linear array real-time transducer was combined with a pulsed Doppler transducer to study and compare the mean blood flow velocity waveform in 77 normal pregnancies and 12 cases of intrauterine growth retardation. All pregnancies were in the third trimester. In normal pregnancies the peak velocity, end diastolic velocity, and pulsatile index remained unchanged with increasing gestational age. End diastolic velocity was lowered or at zero level (high pass filter level), and the pulsatile index was elevated in most cases of severe intrauterine growth retardation. Peak velocity related closely with the quality of the heart rate patterns and the condition of the infant at birth.

Aorta, Thoracic↗

Production of inflammatory mediators and cytokine responsiveness of an SV40-transformed human proximal tubular epithelial cell line.

Proximal tubular epithelial cells (PTEC) play a central role in the physiology of the renal tubulointerstitium. To be able to study the relationship between tubular cells and inflammatory renal diseases the availability of cultured cells is of importance. This study describes an immortalized proximal tubular epithelial cell line which was generated using SV40 DNA. To determine whether the transformation altered the cell line, the transformed cell line was characterized phenotypically using different monoclonal antibodies directed against peptidases, which are characteristic of PTEC, such as adenosine deaminase binding protein (CD26), leucine amino peptidase and carboxy peptidase M by immunofluorescent staining and FACS analysis. All peptidases were clearly present on the parental cell line and the transformed cell line. However, the level of expression of the peptidases was lower on the transformed cell line as compared to the parental nontransfected cells. The morphology of the transformed cell line, determined using a transwell culture system and electron microscopy, showed a polarized morphology of the tubular cells, tight junctions and microvilli. The transformed cell line was compared with the parental proximal tubular epithelial cells in its ability to respond to inflammatory cytokines such as IL- 1alpha TNF-alpha, IFN-gamma. Stimulation with these cytokines resulted in enhanced production of complement components C2, C3, C4 and factor H, IL-6 and the chemokines IL-8 and MCP-1. The transformed cell line responded in a similar fashion as the parental cell line, although the amount of the different proteins produced was significantly higher in the transformed cell line. Overall, the transformed tubular cell line seems to be a suitable model to study different effects on tubular cells in relation to inflammatory kidney diseases.

Blotting, Southern↗

Tubular epithelial cells: A critical cell type in the regulation of renal inflammatory processes.

Most chronic human kidney diseases are characterized by a final common pathway consisting of interstitial inflammation and ultimately leading to interstitial fibrosis. Within this process, tubular epithelial cells (TECs) play a critical role. Both in vitro and in vivo it has been demonstrated that TECs are an important source of various cytokines, chemokines, growth factors, adhesion molecules and extracellular matrix components. In the present review we will outline the capacity of TECs to produce inflammatory mediators and discuss the different mechanisms involved in the regulation of production of these mediators.

Animals↗

Immunological function of tubular epithelial cells: the functional implications of CD40 expression.

Tubulo-interstitial inflammation in the kidney is characterized by the presence of activated T cells. Both by the local production of cytokines, as well as by direct cell-cell interactions, these activated T cells might affect the immune and inflammatory response. Recently it has been demonstrated that these kidney-infiltrating T cells express CD40 ligand and that tubular epithelial cells (TECs) express CD40. In the present review we will discuss the potential implications of CD40-CD40L interactions for the activation of TECs and its immunological function.

Animals↗

Isolation, culture, characterization and use of human renal tubular epithelial cells.

Tubulointerstitial alterations are a hallmark of most renal diseases. In vitro culture of different cell types of the tubulointerstitial compartment have been instrumental in studying their respective contributions to the inflammatory and fibrotic process. The present paper provides an overview of the isolation, culture and characterization of tubular epithelial cells, with a main emphasis on cells from human origin.

Cell Culture Techniques↗

Both naive and memory T cells can provide help for human IgE production, but with different cytokine requirements.

Most in vitro systems for the induction of IgE production by human B cells require both IL-4 and the presence of T cells. Little is known about the mechanism of T cell help or the ability of different T cell subsets to provide this helper activity. In the present study we demonstrate that, in the presence of exogenous IL-4, anti-CD3 stimulated naive T cells (CD4+CD45RA+) are potent helper cells for human IgE production. In their presence, as little as 750 autologous B cells can produce up to 100 ng/ml IgE. This response was found over a broad range of anti-CD3 concentrations. IgE helper activity by naive T cells was inhibited by IL-2. Under all conditions tested, naive T cells were unable to provide help for IgM production. This is in contrast to activated memory T cells (CD4+CD45RO+), which are very efficient helper cells for IgM or IgE production, provided that IL-2 or IL-2 plus IL-4 are present respectively.

Antibodies, Monoclonal↗