Production Of Mediators In Response Research Articles

Spironolactone inhibits production of proinflammatory mediators in response to lipopolysaccharide via inactivation of nuclear factor-κB

The effect of spironolactone (SPIR) on lipopolysaccharide (LPS)-induced production of proinflammatory mediators was examined using RAW 264.7 macrophage-like cells and mouse peritoneal macrophages. SPIR significantly inhibited LPS-induced production of nitric oxide (NO), tumor necrosis factor-α and prostaglandin E2. The inhibition was not mediated by cell death. SPIR reduced the expression of an inducible NO synthase mRNA in response to LPS. SPIR significantly inhibited phosphorylation of p65 nuclear factor (NF)-κB in response to LPS. Furthermore, SPIR inhibited phosphorylation of IκB kinase (IKK) as an upstream molecule of NF-κB in response to LPS. LPS did not induce the production of aldosterone in RAW 264.7 cells. Taken together, SPIR is suggested to inhibit LPS-induced proinflammatory mediators via inactivation of IKK/NF-κB in LPS signaling.

Role of TLR-2 and Fungal Surface Antigens on Innate Immune Response Against Sporothrix schenckii

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2-/- animals. The results showed that TLR-2-/- animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2-/-. The absence of TLR-2 led to lower production of the cytokines TNF-α, IL-1β, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii.

Increased expression of IL-1 receptors in response to IL-1β may produce more IL-6, IL-8, VEGF, and PGE2 in senescent synovial cells induced in vitro than in presenescent cells

Primary synovial cells with high passage number demonstrate increased production of proinflammatory mediators in response to inflammatory stimuli compared with cells with low passage number. This study used synovial cells to learn how different numbers of serial subculture passages affect the production of proinflammatory mediators in response to interleukin (IL)-1β. Synovial cells were serially subcultured in flasks until passage 7. During cell passage, synovial cells were treated with IL-1β for 24 h. Levels of proinflammatory mediators were analyzed by ELISA, real-time PCR, and Western blot. Synovial cells at passage 7 had elongated morphology and higher activity of β-galactosidase, a marker of senescence, than those at passage 3. Production of IL-6, IL-8, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE(2)) in response to IL-1β was significantly increased in cells at passage 7 compared with passage 3. To evaluate the mechanism of this different response, IL-1 receptor expression was studied in cells stimulated with IL-1β. Compared with cells at passage 3, cells at passage 7 had stronger expression of IL-1 receptors 1 and 2, as well as significantly increased expression of both receptors, in response to IL-1β. This finding suggests that differential production in response to inflammatory stimuli associated with cell passages should be considered when in vitro experiments are used to evaluate the production levels of proinflammatory mediators.

103. Activated Macrophagelike THP-1 Cells Modulate Annulus Fibrosus Cell Production of Inflammatory Mediators in Response to Cytokines

103. Activated Macrophagelike THP-1 Cells Modulate Annulus Fibrosus Cell Production of Inflammatory Mediators in Response to Cytokines

Adhesion-dependent activation of mucosal interleukin-6 production

Mucosal exposure to Escherichia coli elicits an inflammatory response in the urinary tract. Interleukin-6 (IL-6) is secreted into the urine, and polymorphonuclear leukocytes (PMNLs) are recruited to the site of infection. This study analyzed the ability of mucosally administered bacterial components to activate IL-6 and PMNL responses. P, S, and type 1 fimbrial preparations with adhesins specific for Gal alpha 1-4Gal beta, NeuAc alpha 2-3Gal, and mannose, respectively, were inoculated intravesically into lipopolysaccharide (LPS)-responder (C3H/HeN) and LPS-nonresponder (C3H/HeJ) mice. The role of the fimbrial adhesin was examined by comparing P and S fimbriae with (Adh+) and without (Adh-) the receptor-binding domain. Isolated lipid A was used in parallel. The urinary IL-6 levels were elevated after challenge with Adh+ P fimbriae, but not after challenge with the Adh- P fimbriae, Adh+ or Adh- S fimbriae, or type 1 fimbriae. The activation was not a function of contaminating LPS, since it occurred in both LPS-responder and -nonresponder mice and since isolated lipid A was a poor activator of the IL-6 response. In contrast, lipid A was a potent inducer of the PMNL response. The results suggested that the IL-6 and PMNL responses were activated via different pathways; the IL-6 response was activated mainly by an adhesion-dependent interaction with the mucosa, and the PMNLs were activated mainly by lipid A. The results emphasize the active role of the mucosal barrier in the production of mediators in response to diverse bacterial stimulants.