Chlamydiae components and signaling pathway(s) responsible for the production of proinflammatory cytokines by human monocytes/macrophages are not clearly identified. To this aim, Chlamydia trachomatis-inactivated elementary bodies (EB) as well as the following seven individual Ags were tested for their ability to induce the production of proinflammatory cytokines by human monocytes/macrophages and THP-1 cells: purified LPS, recombinant heat shock protein (rhsp)70, rhsp60, rhsp10, recombinant polypeptide encoded by open reading frame 3 of the plasmid (rpgp3), recombinant macrophage infectivity potentiator (rMip), and recombinant outer membrane protein 2 (rOmp2). Aside from EB, rMip displayed the highest ability to induce release of IL-1β, TNF-α, IL-6, and IL-8. rMip proinflammatory activity could not be attributed to Escherichia coli LPS contamination as determined by the Limulus Amoebocyte lysate assay, insensitivity to polymyxin B (50 μg/ml), and different serum requirement. We have recently demonstrated that Mip is a “classical” bacterial lipoprotein, exposed at the surface of EB. The proinflammatory activity of EB was significantly attenuated in the presence of polyclonal Ab to rMip. Native Mip was able to induce TNF-α and IL-8 secretion, whereas a nonlipidated C20A rMip variant was not. Proinflammatory activity of rMip was unaffected by heat or proteinase K treatments but was greatly reduced by treatment with lipases, supporting a role of lipid modification in this process. Stimulating pathways appeared to involve TLR2/TLR1/TLR6 with the help of CD14 but not TLR4. These data support a role of Mip lipoprotein in pathogenesis of C. trachomatis-induced inflammatory responses.
SUMMARYThe effects exerted on the (i-receptors of the pineal gland of two types of experimental manipulation known to acutely modify hypothalamic function in the female rat have been investigated. The sensitivity of the pinealocytes towards norepinephrine was monitored by measuring N-acetyl transferase activity as well as the production of melatonin. The use of a new radioimmunoassay for melatonin enabled us to carry out both determinations on the same gland obtained from in vivo experiments.Firstly, unilateral electrochemical brain lesions, placed stereotaxically into the median eminence of 23 day old female rats leads to premature ovulation on day 27 or day 2 8 of life. We report here that this precocious maturation of the hypothalamic-gonadal axis is accompanied by a significant increase, first observable on day 2 6, in the sensitivity of the pinealocyte [3-receptors toward norepinephrine ( 1O -6 M) in vitvo.Secondly, neonatal a sterilization » of female rats using estradiol benzoate ( 100 t i g per rat ; day 4 ) known to lead to permanent neuroendocrine abnormalities in adulthood, also led to an increase in sensitivity of the pineal towards norepinephrine. By day 45 of life, norepinephrine stimulation of N-acetyl transferase activity was significantly more effective in treated animals than in controls. This effect could still be observed at 90 days.The mechanisms underlying these unexpected observations remain obscure.
Precocious sexual maturation was induced in immature female rats by 2 types of unilateral hypothalamic lesions. Stainless steel electrodes produced smaller tissue defects but proved more efficient than platinum electrodes.
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