TNFRp55 modulates IL-6 and nitric oxide responses following Yersinia lipopolysaccharide stimulation in peritoneal macrophages

Autor: Gabriel A. Rabinovich, María Silvia Di Genaro, Ricardo Javier Eliçabe, Jose Luis Arias
Rok vydání: 2011
Předmět:
Lipopolysaccharides
Lipopolysaccharide
Ciencias de la Salud
Yersinia
Oligodeoxyribonucleotides
Antisense
chemistry.chemical_compound
Mice
Immunology and Allergy
Macrophage
TNFRp55
MACROPHAGES
Yersinia enterocolitica
Cells
Cultured
Polymyxin B
Mice
Knockout
NF-kappa B
Hematology
Nitric oxide synthase
Otras Ciencias de la Salud
Medicina Básica
Receptors
Tumor Necrosis Factor
Type I
Tumor necrosis factor alpha
medicine.symptom
Signal Transduction
LPS
CIENCIAS MÉDICAS Y DE LA SALUD
Immunology
Inmunología
Inflammation
Biology
Nitric Oxide
Nitric oxide
TLR
Prohibitins
medicine
Animals
Antigens
Bacterial
Interleukin-6
CYTOKINES
GENE EXPRESSION REGULATION
biology.organism_classification
Molecular biology
Toll-Like Receptor 4
Tumor Necrosis Factor Decoy Receptors
chemistry
Gene Expression Regulation
biology.protein
YERSINIA ENTEROCILITICA
Macrophages
Peritoneal
Zdroj: Immunobiology. 216(12)
ISSN: 1878-3279
Popis: While cytokines are major regulators of macrophage activation following host-pathogen interactions, they also act to limit inflammation to avoid tissue damage. In previous studies we reported the development of progressive Yersinia enterocolitica-induced reactive arthritis (ReA) in mice lacking the tumor necrosis factor receptor p55 (TNFRp55). In this work, we analyzed the response of TNFRp55⁻/⁻ macrophages to Y. enterocolitica antigens. We found higher concentration of nitric oxide (NO) in TNFRp55⁻/⁻ compared to wild-type macrophages in response to heat-killed Yersinia (HKY) and Yersinia outer membranes (OM). Moreover, Toll-like receptor (TLR)4 expression was increased in OM-stimulated TNFRp55⁻/⁻ versus wild-type (WT) macrophages. Accordingly, NO production was inhibited in TLR4-deficient macrophages following stimulation with OM, suggesting that LPS may function as a major OM component implicated in these responses. Thus, augmented NO production together with enhanced expression of inducible nitric oxide synthase (iNOS) and higher IL-6 production, may provide a pro-inflammatory setting in Yersinia LPS-stimulated TNFRp55⁻/⁻ macrophages. Augmented synthesis of NO and IL-6 was prevented by treatment with Polymyxin B, or by exposure to a specific NF-κB p65 oligonucleotide antisense, indicating the involvement of TLR4-mediated NF-κB activation in the unleashed pro-inflammatory response triggered by TNFRp55 deficiency. Thus, TNFRp55 modulates macrophage functions in response to Yersinia LPS stimulation through mechanisms involving NO, IL-6 and NF-κB pathways, suggesting an essential regulatory role of TNF via TNFRp55 signaling. Fil: Eliçabe, Ricardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina Fil: Arias, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentina
Databáze: OpenAIRE
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