Biomedical subjects

Jens Kuipers

Publications and source records attributed to Jens Kuipers.

3 recordsLinked to original sources

PubMed2004

Production of prostaglandin E2 in monocytes stimulated in vitro by Chlamydia trachomatis, Chlamydophila pneumoniae, and Mycoplasma fermentans.

Chlamydia trachomatis (CT) as well as Chlamydophila pneumoniae (CP) cause chronic inflammatory diseases in humans. Persistently infected monocytes are involved in the pathogenesis by inducing mediators of inflammation. An in vitro system of chlamydial persistence in human peripheral blood monocytes (HPBM) was used to investigate prostaglandin E(2) (PGE(2)) production and the expression of the key enzyme for prostaglandin production, cyclooxygenase-2 (COX-2). PGE(2) production was determined by PGE(2)-ELISA of HPBM-culture supernatants. Cox-2 mRNA expression was measured by real-time RT-PCR of total RNA isolated from HPBM. Both, CT and CP, stimulated PGE(2) production of HPBM in vitro. Equivalent numbers of CT per host cell induced a higher PGE(2)-response compared to CP. The amount of synthesized PGE(2) depended on the chlamydial multiplicity of infection (MOI). Even at an MOI of 10 the amount of CT- and CP-induced prostaglandin, respectively, was lower than the amount of prostaglandin induced by E. coli lipopolysaccharide (LPS) at a concentration of 10microg/ml. In contrast to stimulation with LPS, Chlamydia-induced PGE(2) production as well as cox-2 mRNA decreased after day 1 post infection (p.i.). These data indicate that Chlamydia stimulate PGE(2) production in human monocytes. Since Chlamydia are often contaminated by mycoplasma, the influence of mycoplasma on the prostaglandin production was investigated additionally. Mycoplasma fermentans (MF) also stimulated PGE(2) production. The co-infection of mycoplasma and Chlamydia resulted in an additive effect in the production of PGE(2). Thus it is important to use host cells and Chlamydia free of mycoplasma contamination for the analysis of Chlamydia-induced prostaglandin production.

Chlamydia trachomatis↗

PubMed2004

Chlamydia-induced arthritis.

PURPOSE OF REVIEW: Chlamydia-induced arthritis is the most frequent form of reactive arthritis in Western countries. This article gives an overview of the recent findings with respect to diagnosis, pathogenesis, and therapy of the disease. RECENT FINDINGS: Recent advances in the modification and standardization of polymerase chain reaction techniques give promise to identify Chlamydia more frequently from joint samples. Based on the sequenced chlamydial genome, considerable progress has been achieved in the understanding of the Chlamydia-host cell interaction, indicating that persistence is an alternate state of the bacteria used by Chlamydia to escape the immune system of the host rather than a general stress response. Furthermore, Chlamydia has the ability to reprogram the host cell by chlamydial effector proteins, which are transported from the inclusion into the host cell cytoplasm. The role of HLA-B27 is discussed in view of the pathogenesis of the disease. HLA-B27 should be considered a risk factor for chronic and/or axial disease rather than a true susceptibility factor for the development of Chlamydia-induced arthritis. No progress has been made in terms of causative therapy aiming at eradication of the bacteria. Tumor necrosis factor-alpha blocking agents may represent a new option in cases that are refractory to therapy. SUMMARY: Molecular biology not only has improved the ability to detect Chlamydia in the joint for diagnostic purposes but also has extended the current understanding of the pathogenesis of the disease. In contrast to this progress, causative therapy of Chlamydia-induced arthritis is still an unfulfilled need.

Arthritis, Reactive↗

PubMed2002

Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated reactive arthritis.

The aim of this study was to determine whether NK cell receptor (NKR) expression could modulate cytotoxicity of oligoclonal CD8+ T cells present in the synovial fluid (SF) of HLA-B27-reactive arthritis (ReA) patients, especially in a TCRBV1 population shared among different patients and cytotoxic toward HLA-B27. A CD8+ T cell line, two TCRBV1 lines and clones were isolated from the SF of an HLA-B27+ ReA patient, and tested with mAb specific for Ig-like (KIR2DL1, KIR2DL2, KIR3DL1 and ILT2) and CD94 C-type lectin NKR. Transcripts for NKG2 subunits (NKG2A-2E) associated with CD94 were also evaluated. Function was tested in a 51Cr-release cytotoxic assay. We found stable but distinct levels of CD94/NKG2 complexes at the surface of T cell lines and clones. Different NKG2 members could be associated with CD94, either inhibitory (NKG2A/B) or activating (NKG2C). The inhibitory ILT2 receptor could also be differently expressed, but other Ig-like NKR were negative. Functionally, one TCRBV1 line and clones with a high CD94/NKG2A expression did not lyse B27+ targets. Another TCRBV1 line with the same TCRBV1 rearrangement had a low expression of CD94/NKG2A, but expressed NKG2C transcripts and was cytotoxic toward HLA-B27. HLA-B27 is a ligand for ILT2 and we observed an inhibitory effect of ILT2 engagement on B*2705 targets in blockade experiments. Altogether, these data indicate a high degree of heterogeneity in the expression of NKR by intrasynovial CD8+ T cells which could modulate their cytotoxicity and play a role in the control of this HLA class I-associated autoimmune disease.

Antibodies, Monoclonal↗