Ricin induces the production of tumour necrosis factor-alpha and interleukin-1 beta by human peripheral-blood mononuclear cells.
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ABSTRACT:
SUBMITTER: Licastro F
PROVIDER: S-EPMC1134485 | biostudies-other | 1993 Sep
REPOSITORIES: biostudies-other
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Project description:To evaluate the inflammatory state in Crohn's disease (CD) patients and correlate it with genetic background and microbial spreading.By means of flow cytometry, production of tumor necrosis factor-alpha (TNF-?) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis (UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants (R702W, G908R and L1007Pfs*2) and basal production of TNF-? was correlated to NOD2 genotype. Also, production of TNF-? was correlated to plasmatic levels of LPS Binding Protein (LBP), soluble (s) CD14 and to the activity state of the disease.The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-? compared with healthy subjects and UC patients, and after stimulation with Pam3CSK4 (ligand of TLR2/1) and MDP-L18 (ligand of NOD2) this difference was maintained, while other microbial stimuli (LPS, ligand of TLR4 and PolyI:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF-? between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-? production did not show a clear correlation with either LBP or sCD14 levels in plasma. Moreover, no clear correlation was seen between TNF-? production and activity indices in either CD or UC.Peripheral monocytes from CD express higher basal and stimulated TNF-? than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.
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Project description:We report here the characterization of a novel Leishmania infantum protein termed papLe22 (22-kDa potentially aggravating protein of Leishmania). A positive clone from a cDNA library was identified by serum of a visceral leishmaniasis (VL) patient. Full-length cDNA obtained using rapid amplification of cDNA ends-PCR codes for a 22-kDa protein. In L. infantum promastigotes an endogenous nuclear protein of 14-kDa electrophoretic mobility was found by using an antiserum prepared against the fusion protein glutathione S-transferase-papLe22. Its expression was also shown in L. infantum amastigotes and in Leishmania major and Leishmania guyanensis promastigotes. VL patients' sera showed anti-papLe22 immunoglobulin M (IgM) and IgG reactivities, indicating that a primary response against the leishmanial protein papLe22 accompanied acute VL manifestations. Specific IgG levels were correlated with patients' clinical status. The presence of IgG1, IgG2, and IgG3 subclasses suggested a mixed Th1- and Th2-type response; there was no correlation between subclass reactivity and the disease course. The recombinant papLe22 specifically activated interleukin-10 production by VL patients' peripheral blood mononuclear cells collected at diagnosis and after treatment-induced cure, indicating its contribution to VL pathogenesis and concomitant immunosuppression and its potential role in the reactivation of latent parasites. As a dominant immunogen, papLe22 might be used as a vaccine component, provided that the vaccination protocol directs the response toward the Th1 pattern.
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