Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.64 (proteinase K)
 4,071 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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-1beta, TNF-alpha, 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 microg/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-alpha 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.
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PMID:The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14. 1817 56

Streptococcus suis causes invasive infections in pigs and occasionally in humans. Worldwide, S. suis serotype 2 is most frequently isolated from diseased piglets, but the less virulent serotype 9 is emerging, at least in Europe. We compared the activation of human Toll-like receptors (hTLRs) by S. suis serotype 2 and 9 strains to better understand the role of the innate immune response in fighting S. suis infections. Neither live nor heat-killed log phase grown S. suis activated the hTLR1/2, hTLR2/6 and hTLR4/MD-2 complexes. However, the hTLR2/6 complex was specifically activated by both serotypes after disruption of the cell wall synthesis using penicillin. Activation levels of the hTLR2/6 complex were higher for serotype 9 strains compared to serotype 2 strains suggesting intrinsic differences in cell wall composition between both serotypes. The hTLR2/6 activating fractions decreased in molecular size after digestion with proteinase K and were sensitive for lipoprotein lipase digestion and NaOH hydrolysis, indicating lipoprotein(s) as active component(s). Overall, our results indicate that S. suis lipoproteins activate TLR2/6 but not TLR1/2 and that the clinically different serotypes 2 and 9 display differential release of TLR ligand when cell wall integrity is compromised.
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PMID:Differential activation of the Toll-like receptor 2/6 complex by lipoproteins of Streptococcus suis serotypes 2 and 9. 2004 19