Toll-Like Receptors Expression and NF-kappa B Activation in Peritoneal Leukocytes in Morphine-Mediated Impairment of Zymosan-Induced Peritonitis in Swiss Mice

作者：Wypasek Ewa^*; Natorska Joanna; Mazur Agnieszka Irena; Kolaczkowska Elzbieta

来源：Archivum Immunologiae et Therapiae Experimentalis, 2012, 60(5): 373-382.

DOI：10.1007/s00005-012-0186-x

• Peritonitis
• NF-kappa B
• TLR
• Morphine
• Mice

Zymosan-induced peritonitis represents a well-described model of acute inflammation. The binding of zymosan with its specific Toll-like receptors (TLR2 and TLR6) on leukocytes initiates activation and phosphorylation of nuclear factor (NF)-kappa B, which leads to accumulation of NF-kappa B p65 subunits in the nucleus and subsequently up-regulation of the proinflammatory cytokine genes expression. Intraperitoneal co-administration of zymosan and morphine significantly inhibits peritonitis in several strains of mice by decreasing the influx of exudatory cells; however, mechanisms of this action still remain unclear. We aimed to verify the effects of morphine on NF-kappa B and TLRs expression at messenger RNA and protein levels during the early stages of zymosan-induced peritonitis. Peritonitis was induced by a single injection of zymosan A or zymosan supplemented with morphine in Swiss mice. At selected time points, after stimulation, peritoneal leukocytes were harvested. The TLRs and NF-kappa B expression was assessed by real-time PCR and flow cytometry. In comparison with the mice injected with zymosan only, morphine co-injection significantly decreased the expression of phospho-NF-kappa B and TLR2 in all investigated immunocompetent cells as well as up-regulated the levels of nitric oxide (NO) in peritoneal fluid. Moreover, supplementation of zymosan with morphine altered the TLR, NF-kappa B and some proinflammatory cytokines (keratinocyte-derived chemokine, tumor necrosis factor-alpha) gene expression during ongoing inflammation. We may postulate that after morphine stimulation peritoneal leukocytes recognize less effectively zymosan antigens because of impaired TLRs expression. The lower TLR expression attenuates TLR-mediated signal transduction, which prevents NF-kappa B activation. Additionally, during zymosan-induced peritonitis, morphine may modulate the NF-kappa B expression, at least partially, by an up-regulated release of NO, as suggested by others.

• 出版日期2012-10