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Inflammatory Cytokine Levels (inflammatory + cytokine_level)
Selected AbstractsTNF Alpha,308 Genotype and Renin,Angiotensin System in Hemodialysis Patients: An Effect on Inflammatory Cytokine Levels?ARTIFICIAL ORGANS, Issue 2 2005Gultekin Genctoy Abstract:, Background: Renin,angiotensin system (RAS) was suggested to modulate inflammatory cytokine production. Angiotensin II was consistently shown to increase production of tumor necrosis factor alpha (TNF-,). However, inflammatory cytokines and RAS were modulated by genetic polymorphisms such as TNF-,,308 G > A and angiotensin-converting enzyme (ACE) I/D gene polymorphisms. The aim of this study was to investigate the effects of ACE and TNF-, genotypes on inflammatory cytokines in hemodialysis (HD) patients. Methods: ACE I/D and TNF-,,308 G > A genotypes, pre- and postdialysis plasma renin activity (PRA), serum ACE, interleukin-1 beta (IL-1,), and TNF-, levels were determined in 22 HD patients. Results: Predialysis serum ACE activity is correlated with TNF-, (r = 0.63; P = 0.01), and PRA was correlated with IL-1, levels (r = 0.49; P = 0.02). Pre/postdialysis IL-1, and TNF-, were similar in DD and II/ID ACE genotypes. Predialysis TNF-, and IL-1, (32.4 ± 5; 35.1 ± 4.2 vs. 28.1 ± 3.7; 26.5 ± 6.2 pg/mL; P < 0.05) and postdialysis TNF-, levels (30.4 ± 1.4 vs. 28.4 ± 0.82 pg/mL; P < 0.05) were significantly higher in TNF1/2 than TNF1/1 patients. Conclusion: ACE and TNF-,,308 G > A (1/2) gene polymorphisms may contribute to modulation of proinflammatory cytokine production and hence chronic inflammation in HD patients. [source] Involvement of endotoxin in the mortality of mice with gut-derived sepsis due to methicillin-resistant Staphylococcus aureusMICROBIOLOGY AND IMMUNOLOGY, Issue 6 2010Masashi Uramatsu ABSTRACT MRSA causes a wide diversity of diseases, ranging from benign skin infections to life-threatening diseases, such as sepsis. However, there have been few reports of the pathophysiology and mechanisms of sepsis resulting from the gut-derived origin of MRSA. Therefore, we established a murine model of gut-derived sepsis with MRSA and factors of MRSA sepsis that cause deterioration. We separated mice into four groups according to antibiotic treatment as follows: (i) ABPC 40 mg/kg; (ii) CAZ 80 mg/kg; (iii) CAZ 80 mg/kg + endotoxin 10 ,g/mouse; and (iv) saline-treated control groups. Gut-derived sepsis was induced by i.p. injection of cyclophosphamide after colonization of MRSA strain 334 in the intestine. After the induction of sepsis, significantly more CAZ-treated mice survived compared with ABPC-treated and control groups. MRSA were detected in the blood and liver among all groups. Endotoxin levels were significantly lower in the CAZ-treated group compared to other groups. Inflammatory cytokine levels in the serum were lower in the CAZ-treated group compared to other groups. Fecal culture showed a lower level of colonization of E. coli in the CAZ-treated group compared to other groups. In conclusion, we found that CAZ-treatment ameliorates infection and suppresses endotoxin level by the elimination of E. coli from the intestinal tract of mice. However, giving endotoxin in the CAZ-treated group increased mortality to almost the same level as in the ABPC-treated group. These results suggest endotoxin released from resident E. coli in the intestine is involved in clinical deterioration resulting from gut-derived MRSA sepsis. [source] Regulation of lipopolysaccharide-induced inflammatory response and endotoxemia by ,-arrestins,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Katie J. Porter ,-Arrestins are scaffolding proteins implicated as negative regulators of TLR4 signaling in macrophages and fibroblasts. Unexpectedly, we found that ,-arrestin-1 (,-arr-1) and -2 knockout (KO) mice are protected from TLR4-mediated endotoxic shock and lethality. To identify the potential mechanisms involved, we examined the plasma levels of inflammatory cytokines/chemokines in the wild-type (WT) and ,-arr-1 and -2 KO mice after lipopolysaccharide (LPS, a TLR4 ligand) injection. Consistent with lethality, LPS-induced inflammatory cytokine levels in the plasma were markedly decreased in both ,-arr-1 and -2 KO, compared to WT mice. To further explore the cellular mechanisms, we obtained splenocytes (separated into CD11b+ and CD11b, populations) from WT, ,-arr-1, and -2 KO mice and examined the effect of LPS on cytokine production. Similar to the in vivo observations, LPS-induced inflammatory cytokines were significantly blocked in both splenocyte populations from the ,-arr-2 KO compared to the WT mice. This effect in the ,-arr-1 KO mice, however, was restricted to the CD11b, splenocytes. Our studies further indicate that regulation of cytokine production by ,-arrestins is likely independent of MAPK and I,B,-NF,B pathways. Our results, however, suggest that LPS-induced chromatin modification is dependent on ,-arrestin levels and may be the underlying mechanistic basis for regulation of cytokine levels by ,-arrestins in vivo. Taken together, these results indicate that ,-arr-1 and -2 mediate LPS-induced cytokine secretion in a cell-type specific manner and that both ,-arrestins have overlapping but non-redundant roles in regulating inflammatory cytokine production and endotoxic shock in mice. J. Cell. Physiol. 225: 406,416, 2010. © 2010 Wiley-Liss, Inc. [source] Over-expression of I,B-kinase-, (IKK,/IKKi) induces secretion of inflammatory cytokines in prostate cancer cell linesTHE PROSTATE, Issue 7 2009Benjamin Péant Abstract BACKGROUND Elevated inflammatory cytokine levels in serum have been associated with advanced stage metastasis-related morbidity in prostate cancer. Several studies have shown that IL-6 and IL-8 can accelerate the growth of human prostate cancer cell lines. Previous studies, in murine embryonic fibroblasts, have shown that I,-B kinase-epsilon (IKK,/IKKi)-deficiency results in the reduction of lipopolysaccharide-mediated expression of IL-6. RESULTS In this study, we report that over-expression of IKK, in hormone-sensitive 22Rv1 and LNCaP prostate cancer cells induces the secretion of several inflammatory cytokines including IL-6 and IL-8. Both of these cytokines are secreted by hormone-refractory PC-3 prostate cancer cells and IKK, knock-down in these cells correlates with a strong decrease in IL-6 secretion. Furthermore, we demonstrate that IKK, over-expression does not induce the activation of the IKK, classical targets NF-,B and IRF-3, two transcription factors involved in the regulation of several cytokines. Finally, we observe that high IKK, expression results in its nuclear translocation, a phenomena that is TBK1-independent. CONCLUSIONS This study identifies IKK, as a potential prostate cancer gene that may favor chronic inflammation and create a tumor-supporting microenvironment that promotes prostate cancer progression, particularly by the induction of IL-6 secretion that may act as a positive growth factor in prostate cancer. Prostate 69: 706,718, 2009. © 2009 Wiley-Liss, Inc. [source] A20 suppresses inflammatory responses and bone destruction in human fibroblast-like synoviocytes and in mice with collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 8 2010Young-Sool Hah Objective Nuclear factor-,B (NF-,B) has been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). The purpose of this study was to determine whether A20, a universal inhibitor of NF-,B, might have antiarthritic effects. Methods An adenovirus containing A20 complementary DNA (AdA20) was used to deliver A20 to human rheumatoid fibroblast-like synoviocytes (FLS) in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via intraarticular injection into the ankle joints bilaterally. Results In vitro experiments demonstrated that AdA20 suppressed NF-,B activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor , in FLS. Mice with CIA that were treated with AdA20 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels, than did control virus,injected mice. The protective effects of AdA20 were mediated by the inhibition of the NF-,B signaling pathway. The severity of arthritis was also significantly decreased in the untreated front paws, indicating a beneficial systemic effect of local suppression of NF-,B. Surprisingly, mice treated with AdA20 after the onset of CIA had significantly decreased arthritis severity from the onset of clinical signs to the end of the study. Conclusion These results suggest that using A20 to block the NF-,B pathway in rheumatoid joints reduces both the inflammatory response and the tissue destruction. The development of an immunoregulatory strategy based on A20 may therefore have therapeutic potential in the treatment of RA. [source] Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritisARTHRITIS & RHEUMATISM, Issue 10 2009Timothy M. Griffin Objective To test the hypothesis that obesity resulting from deletion of the leptin gene or the leptin receptor gene results in increased knee osteoarthritis (OA), systemic inflammation, and altered subchondral bone morphology. Methods Leptin-deficient (ob/ob) and leptin receptor,deficient (db/db) female mice compared with wild-type mice were studied, to document knee OA via histopathology. The levels of serum proinflammatory and antiinflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by microfocal computed tomography, and body composition was quantified by dual x-ray absorptiometry. Results Adiposity was increased by ,10-fold in ob/ob and db/db mice compared with controls, but it was not associated with an increased incidence of knee OA. Serum cytokine levels were unchanged in ob/ob and db/db mice relative to controls, except for the level of cytokine-induced neutrophil chemoattractant (keratinocyte chemoattractant; murine analog of interleukin-8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis. Conclusion Extreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increasing the incidence of knee OA. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration, because adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee OA in female C57BL/6J mice. These results imply a pleiotropic role of leptin in the development of OA by regulating both the skeletal and immune systems. [source] Manipulation of the small intestine as a cause of the increased inflammatory response after open compared with laparoscopic surgery,,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2006N. Hiki Background: Laparoscopic surgery of the gastrointestinal tract involves a reduced immune response compared with open surgery. The aim of this study was to assess manual handling of the gut in open procedures as the principal cause of the enhanced immune response. Methods: Eighteen Landrace pigs underwent gastrectomy by three different methods: conventional open wound with bowel manipulation, laparoscopically assisted gastrectomy, and gastrectomy without manipulation using a combination of open wound and laparoscopic surgical devices. Local inflammatory changes were assessed by ascites formation, intestinal adhesion development and intestinal inflammatory gene expression. Associated systemic inflammatory changes were determined by measuring portal and systemic plasma endotoxin levels, plasma inflammatory cytokine levels, liver inflammatory gene expression and transaminase levels. Results: Significantly more postoperative intra-abdominal fluid and adhesions were seen in the open group. The expression of inflammatory cytokines was significantly greater in the intestine and liver in the open group. Portal and systemic levels of endotoxin, inflammatory cytokines and transaminases were also higher. Conclusion: Manual handling of organs during gastrectomy is an important contributor to the molecular and humoral inflammatory response to surgery, supporting the use of minimally invasive techniques in gastrointestinal surgery. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||