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Post by LymeEnigma on Jun 3, 2008 8:51:29 GMT -8
Propensity to excessive proinflammatory response in chronic Lyme borreliosis * KAI E. KISAND,11Department of Immunology, Institute of General and Molecular Pathology, Centre of Molecular and Clinical Medicine, * TIINA PRÜKK,22Department of Infectious Diseases, University of Tartu, * KALLE V. KISAND,11Department of Immunology, Institute of General and Molecular Pathology, Centre of Molecular and Clinical Medicine, * SIIRI-MERIKE LÜÜS,33Neurology Clinic of Tartu University Hospital, Tartu, Estonia * IRJA KALBE33Neurology Clinic of Tartu University Hospital, Tartu, Estonia and * RAIVO UIBO11Department of Immunology, Institute of General and Molecular Pathology, Centre of Molecular and Clinical Medicine, * 1Department of Immunology, Institute of General and Molecular Pathology, Centre of Molecular and Clinical Medicine, 2Department of Infectious Diseases, University of Tartu, 3Neurology Clinic of Tartu University Hospital, Tartu, Estonia Kai Kisand, Department of Immunology, Institute of General and Molecular Pathology, University of Tartu, Ravila Str. 19, Tartu 50411, Estonia. e-mail: Kai.Kisand@ut.ee Received 26 June 2006. Accepted 16 October 2006. Kisand KE, Prükk T, Kisand KV, Lüüs SM, Kalbe I, Uibo R. Propensity to excessive proinflammatory response in chronic Lyme borreliosis. APMIS 2007;115:134–41. Abstract: The clinical course of Lyme borreliosis is extremely variable. However, all the clinical manifestations, acute or chronic, are characterized by strong inflammation. Borrelia burgdorferi can induce the production of several proinflammatory and anti-inflammatory cytokines. The aim of our study was to find out whether the balance between inflammatory and regulatory mechanisms is important in determining the course of Lyme borreliosis. 13 patients with early Lyme borreliosis, 8 patients with chronic Lyme disease with neurological or joint manifestations, and 15 age- and sex-matched healthy controls were studied. Chronic forms of Lyme borreliosis were characterized by stronger TNF-α response by monocytes to lipopolysaccharide as well as to borrelia antigen compared to early Lyme borreliosis and the healthy state. The percentage of IL-10-secreting monocytes in response to borrelia lysate was lower in the Lyme borreliosis patients than in healthy controls. The percentage of CD4+ CTLA-4+ regulatory T cells showed the highest values in early Lyme borreliosis. We conclude that chronic forms of Lyme borreliosis can evolve due to an aberrant innate proinflammatory response. www.blackwell-synergy.com/doi/abs/10.1111/j.1600-0463.2007.apm_538.x
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Post by LymeEnigma on Jun 3, 2008 8:52:42 GMT -8
Phagocytosis of Borrelia burgdorferi and Treponema pallidum Potentiates Innate Immune Activation and Induces Gamma Interferon Production{triangledown} Meagan W. Moore,1 Adriana R. Cruz,1 Carson J. LaVake,1 Amanda L. Marzo,1,{dagger} Christian H. Eggers,1 Juan C. Salazar,3 and Justin D. Radolf1,2* Departments of Medicine,1 Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030-3715,2 Division of Pediatric Infectious Diseases, Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut 061063 Received 18 October 2006/ Returned for modification 17 November 2006/ Accepted 2 January 2007 "In contrast to live B. burgdorferi, which elicited a strong inflammatory response even at a spirochete-to-cell ratio of 1:1, monocyte activation and cytokine production in response to live T. pallidum were significantly above background only at MOIs of 10:1 or greater. Furthermore, compared to B. burgdorferi, live T. pallidum induced significantly less surface expression of CD40 and CD83 by monocytes (Fig. 4A), decreased production of TNF-{alpha} and IL-1ß (Fig. 4B) and IL-6 (data not shown), and no IFN-{gamma} (see Fig. 6D, left panels)." Full article: iai.asm.org/cgi/content/full/75/4/2046?view=long&pmid=17220323
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Post by LymeEnigma on Jun 3, 2008 8:53:45 GMT -8
Dynamics of Cytokine Production in Human Peripheral Blood Mononuclear Cells Stimulated by LPS or Infected by Borrelia L. JANSKÝ1, P. REYMANOVÁ1, J. KOPECKÝ2 1Faculty of Biology, University of South Bohemia and 2Institute of Parasitology, Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic Received August 20, 2002 Accepted May 7, 2003 Summary To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-α, IL-10 and finally also IL-1β. Productions of IL- 12 and INF-γ are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1β and TNF-α significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-γ were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-γ, besides IL-1β, TNF-α, IL-6 and IL-10. Productions of IL-1β, IL-6 and TNFα increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-γ begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines. www.biomed.cas.cz/physiolres/pdf/52/52_593.pdf
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Post by LymeEnigma on Aug 19, 2008 9:14:19 GMT -8
Concentration of TGF-β1 in the supernatant of peripheral blood mononuclear cells cultures from patients with early disseminated and chronic Lyme borreliosis Grygorczuk S1*, Chmielewski T2, Zajkowska J1, Świerzbińska R1, Pancewicz S 1, Kondrusik M 1, Tylewska-Wierzbanowska S 2, Hermanowska-Szpakowicz T 1 1 Department of Infectious Diseases and Neuroinfections of the Medical University of Białystok, Poland 2 Department of Chlamydiae, Rickettsiae and Zoonotic Spirochetes of the National Institute of Hygiene, Białystok, Poland Abstract Purpose: The aberrant inflammatory response is probably involved in the pathogenesis of chronic Lyme borreliosis, including chronic Lyme arthritis and neuroborreliosis. Transforming growth factor-beta 1 (TGF-β1) is an important anti-inflammatory and immunomodulatory cytokine and its deficient synthesis is linked to exaggerated inflammation and immune response. Material and methods: Peripheral blood mononuclear cells (PBMC) from 25 patients with Lyme borreliosis and 6 controls were incubated for 7 days with suspension of Borrelia afzeli, B. garinii and B. burgdorferi sensu stricto spirochetes. TGF-β1 concentration in culture supernatants was measured with ELISA. Results were analyzed according to disease duration (group I – chronic borreliosis, n=20; group II – early borreliosis, n=5) and clinical form (LA – arthritis, NB – neuroborreliosis). Results: TGF-β1 concentration was increased in supernatants of PBMC cultures of patients with early neuroborreliosis, in comparison with chronic borreliosis and controls. In chronic, but not in early borreliosis, there was a tendency for decrease of TGF-β1 synthesis under stimulation with B. burgdorferi spirochetes. Conclusions: Impaired synthesis of TGF-β1 by mononuclear cells seems to be present in patients with chronic forms of Lyme borreliosis when compared to those with early stage of the disease. It may be a factor contributing to the persistence of inadequate inflammatory response in patients in whom chronic form of the disease develops. Full article: www.advms.pl/?q=system/files/29_52Grygorczuk.pdf
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Post by nyxie63 on Sept 7, 2008 6:55:14 GMT -8
iai.asm.org/cgi/content/abstract/62/9/3663Outer surface lipoproteins of Borrelia burgdorferi stimulate nitric oxide production by the cytokine-inducible pathway. Y Ma, K P Seiler, K F Tai, L Yang, M Woods, and J J Weis Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132. ABSTRACT The outer surface lipoproteins of Borrelia burgdorferi, OspA and OspB, stimulate the production of nitric oxide (NO) by murine bone marrow-derived macrophages from BALB/c, C3H/HeN, and C3H/HeJ mice. Gamma interferon (IFN-gamma) caused a three- to fivefold enhancement of this production of NO, and the L-arginine analog N-guanidino-monomethyl L-arginine inhibited it. Activation of transcription of the inducible NO synthase gene in stimulated macrophages was demonstrated by reverse transcriptase rapid PCR. Although IFN-gamma increased the amount of NO produced in macrophage cultures, it did not cause transcription of the inducible NO synthase gene greater than that seen with the Borrelia proteins. OspA and OspB also induced the production of high levels (40 to 150 ng/ml) of IFN-gamma in cultures of macrophages incubated with interleukin-2 (IL-2)-elicited cells from normal (T and NK cells) and scid (NK cells) mice but not in macrophages or IL-2-elicited cells cultured individually. This suggests that OspA stimulated macrophage production of cytokines, which, in turn, stimulated the production of IFN-gamma by NK and T cells. Reverse transcriptase rapid PCR demonstrated that OspA and sonicated B. burgdorferi stimulated production of several inflammatory cytokines in macrophage cultures, including IL-1, IL-6, IL-12, IFN-beta, and tumor necrosis factor alpha. As tumor necrosis factor alpha, IFN-beta, and IL-12 are potent activators of IFN-gamma production by T and NK cells, their presence in these cocultures could be responsible for the IFN-gamma production. Lymphocytes from infected C3H mice also produced IFN-gamma when stimulated with B. burgdorferi; thus, immune cells may also modulate NO responses. The generation of NO during infection with B. burgdorferi may be important, as NO has potent antimicrobial properties. NO can also be involved in pathological inflammatory processes in which its generation is detrimental to the host. Thus, the colocalization of B. burgdorferi lipoproteins, NO-producing cells, and regulatory cytokines may determine the outcome of infection
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Post by nyxie63 on Sept 7, 2008 7:03:42 GMT -8
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Post by nyxie63 on Sept 7, 2008 7:19:20 GMT -8
While not necessarily lyme-specific, this does propose some interesting info on the inflammatory process of gram-negative bacterial with flagella. Full text at : www.inotekcorp.com/publications/pdf/ipcpub181.pdfFlagellin, a Novel Mediator of Salmonella-Induced Epithelial Activation and Systemic Inflammation: IkBa Degradation, Induction of Nitric Oxide Synthase, Induction of Proinflammatory Mediators, and Cardiovascular Dysfunction1Tonyia Eaves-Pyles,† Kanneganti Murthy,* Lucas Liaudet,2§¶ La´szlo´ Vira´g,* Gary Ross,‡ Francisco Garcia Soriano,3¶ Csaba Szabo´,*¶ and Andrew L. Salzman4*†§ Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, the monomeric subunit of flagella, is a potent proinflammatory species released by Salmonella. Flagellin (1 mg/ml) induces IkBa degradation, NF-kB nuclear translocation, and inducible NO synthase expression in cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce NF-kB activation or NO production by cultured IEC. Antiserum to flagellin blocks NO production in IEC induced by medium conditioned by a variety of motile Gram-negative enteric pathogens (Escherichia coli, Salmonella muenchen, Serratia marcescens, Proteus mirabilis, and Proteus vulgaris). Flagellin, when injected systemically (;10 mg/mouse), induces systemic inflammation characterized by the systemic expression of a range of proinflammatory cytokines and chemokines and of inducible NO synthase. At higher doses (;300 mg/mouse), flagellin induces shock, characterized by hypotension, reduced vascular contractility in mice, and death. The effects of flagellin do not diminish in C3H/HeJ LPS-resistant mice, indicating that the Toll-like receptor-4 receptor is not involved in flagellin’s actions. In LPS-resistant mice, i.p. injection of S. dublin flagellin or medium conditioned by wild-type S. dublin induces serum IFN-g and TNF-a, whereas medium conditioned by aflagellic mutants has no effect. Flagellin can be detected in the blood of rats with septic shock induced by live bacteria at approximately 1 mg/ml. We propose that flagellin released by Gram-negative pathogens may contribute to the inflammatory response by an LPS- and Toll-like receptor-4-independent pathway. The Journal of Immunology, 2001, 166: 1248–1260.
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Post by LymeEnigma on Sept 7, 2008 8:08:22 GMT -8
If flagellin are that dangerous, that would potentially make Bb very dangerous bacteria. Maybe yet another route to explore?
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