LPS-sensory peptide communication in experimental cystitis

2002 ◽  
Vol 282 (2) ◽  
pp. F202-F210 ◽  
Author(s):  
M. R. Saban ◽  
R. Saban ◽  
T. G. Hammond ◽  
M. Haak-Frendscho ◽  
H. Steinberg ◽  
...  

Stimulation of sensory nerves can lead to release of peptides such as substance P (SP) and consequently to neurogenic inflammation. We studied the role of bacterial lipopolysaccharide (LPS) in regulating SP-induced inflammation. Experimental cystitis was induced in female mice by intravesical instillation of SP, LPS, or fluorescein-labeled LPS. Uptake of fluorescein-labeled LPS was determined by confocal analysis, and bladder inflammation was determined by morphological analysis. SP was infused into the bladders of some mice 24 h after exposure to LPS. In vitro studies determined the capacity of LPS and SP to induce histamine and cytokine release by the bladder. LPS was taken up by urothelial cells and distributed systemically. Twenty-four hours after instillation of LPS or SP, bladder inflammation was characterized by edema and leukocytic infiltration of the bladder wall. LPS pretreatment enhanced neutrophil infiltration induced by SP, increased in vitro release of histamine, tumor necrosis factor-α, and interferon-γ, and significantly reduced transforming growth factor-β1 release. These findings suggest that LPS amplifies neurogenic inflammation, thereby playing a role in the pathogenesis of neurogenic cystitis.

2003 ◽  
Vol 198 (10) ◽  
pp. 1517-1525 ◽  
Author(s):  
Arihiro Kano ◽  
Michael J. Wolfgang ◽  
Qian Gao ◽  
Joerg Jacoby ◽  
Gui-Xuan Chai ◽  
...  

Endothelial cells (ECs) are believed to be an important component in the protection from lipopolysaccharide (LPS)-induced endotoxic shock. However, the cellular and molecular mechanism is not well defined. Here, we report that signal transducer and activator of transcription (STAT) 3 is an essential regulator of the antiinflammatory function of ECs in systemic immunity. Because STAT3 deficiency results in early embryonic lethality, we have generated mice with a conditional STAT3 deletion in endothelium (STAT3E−/−). STAT3E−/− mice are healthy and fertile, and isolated ECs initiate normal tube formation in vitro. Conditional endothelial but not organ-specific (i.e., hepatocyte or cardiomyocyte) STAT3 knockout mice show an increased susceptibility to lethality after LPS challenge. The LPS response in STAT3E−/− mice shows exaggerated inflammation and leukocyte infiltration in multiple organs combined with elevated activity of serum alanine aminotransferase and aspartate aminotransferase, indicating organ damage. Concomitantly, proinflammatory cytokines are produced at an exaggerated level and for a prolonged period. This defect cannot be explained by lack of antiinflammatory cytokines, such as interleukin 10 and transforming growth factor β. Instead, we have shown that a soluble activity derived from endothelia and dependent on STAT3 is critical for suppression of interferon γ. These data define STAT3 signaling within endothelia as a critical antiinflammatory mediator and provide new insight to the protective function of ECs in inflammation.


2002 ◽  
Vol 196 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Francesco Annunziato ◽  
Lorenzo Cosmi ◽  
Francesco Liotta ◽  
Elena Lazzeri ◽  
Roberto Manetti ◽  
...  

Phenotypic markers, localization, functional activities, and mechanisms of action in vitro of CD4+CD25+ T cells, purified from postnatal human thymuses, were investigated. These cells showed poor or no proliferation in mixed lymphocyte culture (MLC), and suppressed in a dose-dependent fashion the proliferative response to allogeneic stimulation of CD4+CD25− thymocytes. Virtually all CD4+CD25+ thymocytes constitutively expressed cytoplasmic T lymphocyte antigen (CTLA)-4, surface tumor necrosis factor type 2 receptor (TNFR2), and CCR8. They prevalently localized to perivascular areas of fibrous septa and responded to the chemoattractant activity of CCL1/I-309, which was found to be produced by either thymic medullary macrophages or fibrous septa epithelial cells. After polyclonal activation, CD4+CD25+ thymocytes did not produce the cytokines interleukin (IL)-2, IL-4, IL-5, IL-13, interferon γ, and only a very few produced IL-10, but all they expressed on their surface CTLA-4 and the majority of them also transforming growth factor (TGF)-β1. The suppressive activity of these cells was contact dependent and associated with the lack of IL-2 receptor (IL-2R) α-chain (CD25) expression in target cells. Such a suppressive activity was partially inhibited by either anti–CTLA-4 or anti–TGF-β1, and was completely blocked by a mixture of these monoclonal antibodies, which were also able to restore in target T cells the expression of IL-2R α-chain and, therefore, their responsiveness to IL-2. These data demonstrate that CD4+CD25+ human thymocytes represent a population of regulatory cells that migrate in response to the chemokine CCL1/I-309 and exert their suppressive function via the inhibition of IL-2R α-chain in target T cells, induced by the combined activity of CTLA-4 and membrane TGF-β1.


2000 ◽  
Vol 118 (4) ◽  
pp. A479
Author(s):  
Giovanni Corrado ◽  
Alessandra Zicari ◽  
Filiana Nardelli ◽  
Marisa Cavaliere ◽  
Claudia Pacchiarotti ◽  
...  

2003 ◽  
Vol 48 (4) ◽  
pp. 191-193 ◽  
Author(s):  
A. Trattner ◽  
L. Akerman ◽  
M. Lapidoth ◽  
T. Klein ◽  
H. Weiss ◽  
...  

2004 ◽  
Vol 84 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Frédéric Guay, J. Jacques Matte ◽  
Christiane L. Girard ◽  
Marie-France Palin, Alain Giguère ◽  
Jean-Paul Laforest

The effects of a dietary folic acid (B9) supplement on the uterine environment of nulliparous Yorkshire- Landrace (YL) and multiparous Landrace (LD) and multiparous Meishan-Landrace (ML) sows were investigated. Sows were randomly assigned to two treatments: 0 mg kg-1 and 15 mg kg-1 of B9. The supplements were given daily from the estrus preceding insemination up to slaughter on Day 15 of gestation. At slaughter, one uterine horn was used to collect the “uterine flush” and conceptuses in order to determine the uterine content of prostaglandin E2(PGE2) and F2α(PGF2α), estradiol-17β (E2) and transforming growth factor-β2 (TGF-β2), and conceptus expression of cytochrome P450aromatase (P450) and interferon γ mRNA (IFNγ). The other horn was used to determine endometrial expression of interleukin-2 (IL-2), cyclooxygenase-1 (COX1) and -2 (COX2) mRNA and to evaluate endometrial in vitro secretion of PGE2. The B9 supplement tended to decrease the uterine content of PGE2 (P < 0.08), and decrease endometrial expression of COX1 mRNA (P < 0.05). The in vitro secretion of PGE2 was reduced by B9 supplement only in YL sows (P < 0.05). The type of sow did not have any effect on the uterine content of PGE2 (P > 0.10). However, endometrial expression of COX2 mRNA was lower for YL than LD sows (P < 0.05), but there was no difference between ML and LD sows. Endometrial expression of COX1 mRNA was higher for ML than LD sows (P < 0.05). The B9 supplement tended to decrease uterine content of E2 and TGF-β2 in YL and LD sows (P < 0.07), but conceptus expression of P450 mRNA increased only for YL sows (P < 0.05). The uterine content of E2 was lower for YL than LD sows (P < 0.05). The B9 supplement decreased endometrial expression of IL-2 mRNA in LD and YL sows ( P < 0.05), but increased it in ML sows (P < 0.05). Conceptus expression of IFNγ mRNA was not affected either by B9 supplementation or the type of sow. In conclusion, the effect of B9 supplementation on the porcine uterine environment at Day 15 of gestation was influenced by sow type (genotype and/or parity). Key words: Sow, gestation, folic acid, prostaglandin, interleukin-2


FEBS Letters ◽  
1999 ◽  
Vol 442 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Masahiko Yokozeki ◽  
Yoshiyuki Baba ◽  
Hitoyata Shimokawa ◽  
Keiji Moriyama ◽  
Takayuki Kuroda

Author(s):  
Alexander Yu. Bredun ◽  
Oleg F. Melnikov ◽  
Мarina D. Timchenko

Introduction: Chronic inflammatory diseases of the upper respiratory tract of both microbial and viral origin occur due to the immune deficiency of systemic and local nature. Among a large number of immunomodulation agents, a special role belongs to plant preparations, which are characterized by relative harmlessness and high efficiency, both in case of systemic and local use and they are often combined with antimicrobial agents, therefore the aim of the study was to investigate their effect on the reactions and condition of lymphoid cells of tonsilswith separate and combined use in vitro. Methods: Cell suspensions were prepared mechanically and adjusted to a concentration of 2 million/ml in medium 199 with additives. Then, Lizak preparation was added to the cells and starch solution was used in control. Imupret and Esberitox preparations were added to the culture with or without Lizak preparation. After cultivation, the levels of proinflammatory cytokine – Interleukin-1β, pro-allergic factor – Interleukin-4, Th-1 – derivative of cytokine – interferon-γ were studied in the supernatant using the «Tsitokin LLC» reagent kits (RF), as well as tissue regeneration factor – transforming growth factor –TGF-1β (Austria). The preparation was prepared from the cell pellet, in which the relative nonviable cell count was determined in a sample with trypan blue using a light microscope (Olympus CX21FS1).The statistical analysis was performed using Student's t-distribution. Results: Plant-derived preparations did not have any effect on cell viability in culture, did not reduce the level of the pro-inflammatory cytokine interleukin-1β and did not stimulate the production of the regeneration factor TGF-1β. At the same time, the combined use of plant-derived preparations and the antibacterial preparation Lizak in cell culture of tonsils was accompanied by an increase in cell viability compared to the use of Lizak preparation separately, the stimulation of the regulatory antiviral factor interferon-γ and an increase in the production of tissue regeneration factor. Conclusion: The immunomodulating properties of the antibacterial preparation Lizak and plant-derived immunomodulator Esberitox significantly differ in the points of application. Both plant-derived preparations stimulated the production of γ-interferon by tonsil cells in the presence of Lizak preparation, the transforming growth factor TGF-1β, the viability of tonsil cells was the highest with the combination of Lizak and Esberitox.


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