LPS-stimulated TNF-a production

Effects of Various Fatty Acids on LPS-Stimulated TNF-a Production. THP-1 cells were preincubated with n-3 PUFA (EPA... 

EPA Decreases LPS-Induced TNF-a Production. THP-1 cells were pre-incubated with or without EPA before being stimulated by LPS. The levels of secreted TNF-a in cell culture supernatant were determined by ELISA. Without LPS stimulation, no TNF-a production was detected in either the control or EPA-treated cells. LPS-stimulated TNF-a production was significantly decreased by pre-treating cells with EPA (Fig. 2). The decrease of TNF-a production was dose-dependent. 

In lipopolysaccharide (LPS (-treated BV2 microglial cells A3 receptor activation suppresses tumor necrosis factor-a (TNF-a) production by inhibiting PI3K/Akt and NF-kB activation (Lee et al. 2006). Furthermore, it has been reported that in mouse RAW 264.7 cells the A3 receptor inhibits LPS-stimulated TNF-a release by... 

Chitosan also has in vivo stimulatory effect on both nitric oxide production and chemotaxis, and modulates the peroxide production. Chitooligosaccharides (COS) enhanced the migration of the mouse peritoneal macrophages into inflammatory area (Okamoto et al. 2003, Mori et al. 2005, Moon et al. 2007). Yoon et al. (2007) reported that lipopolysaccharide (LPS)-stimulated TNF-a and IL-6 secretion was significantly inhibited in the presence of chitosan oligosaccharide in RAW 264.7 cells. These results suggested that chitosan oligosaccharide may have the anti-inflanunatory effect via the stimulus of TNF-a in the LPS-stimulated inflammation. 

In addition to fish oil, nutrigenomic studies have identified other possible modulators of TNF-a production and/or release in vitro. Kang et al. reported that soybean saponins suppressed the release of TNF-a by LPS-stimulated murine peritoneal macrophages.100 Horrigan et al. demonstrated that concentrations of caffeine that were relevant to human consumption consistently suppressed the production of TNF-a in human blood.101 Clearly, more studies that address the anti-inflammatory effects of food components in studies involving humans are warranted. 

Vulcano M, Alves Rosa MF, Minnucci FS, Chernavsky AC, Isturiz MA N-Formly-methionyl-leucyl-phenylalanine (fMLP) inhibits tumour necrosis factor-alpha (TNF-a) production on lipopolysaccharide (LPS)-stimulated human neutrophils. Clin Exp Immunol 1998 113 39 7. 

Fig.l. Effects of various fatty acids on lipopolysaccharide (LPS)-induced tumor necrosis-factor (TNF)-a production. THP-1 cells preincubated with 60 iM of docosahexaenoic acid (DL), eicosa-pentaenoic acid (EL), arachidonic acid (AL), oleic acid (OL) or stearic acid (SL) for 24 h were stimulated with LPS for 6 h. The amount of TNF-a produced in the control LPS-stimulated cells (L) is set as 100%. TNF-a levels in cell culture supernatant were determined by enzyme-linked immunosorbent assay. Values are means SEM, n = 3. Significantly different from control group (P< 0.05). 

Downregulation of proinflammatory eicosanoids is likely not the only mechanism through which EPA modulates TNF-a production because AA increased LTB and TXB2 levels, but it decreased TNF-a production compared with LPS-stimulated control. In addition to their serving as precursors of eicosanoids, growing evidence has shown that fatty acids can act directly as mediators and modulate signal molecules (43,44). Future research may reveal additional mechanisms that mediate the effects of PUFA on immune responses, thus providing further clarification of the mecha-... 

Mesothelial cells, when stimulated with bacteria or bacterial products, release significant quantities of multiple chemokines, including IL-8, MIP-la and monocyte chemoattractant protein-1 (MCP-1, CCL2) (21-23). When activated by bacterial endotoxin, lipopolysaccharide, IL-lp, or TNF-a, both C-X-C and C-C chemokines are released. The temporal recruitment of specific subpopulations of leukocytes from the vascular compartment to the pleural space depends on a complex balance of soluble cytokines that control the release of chemokines... 

The role of NFkB has been reviewed in ref. 205. NFkB is a key regulator of inflammation, immune responses, cell survival, and cell proliferation inhibition of the NFkB pathway in macrophages leads to more severe atherosclerosis in low density lipoprotein receptor (LDLR) deficient mice, possibly by affecting the pro- and anti-inflammatory balance that controls the development of atherosclerosis (reduced production of LPS-stimulated TNF, and reduction in IL-10) (206). 

Figure 3. Inhibition ofLPS stimulated IL-lfi and TNF-a production from human PBMCS by HMP. The human PBMCs (0.5 XI(f/mL) were cultured with LPS (10 ng/mL) either alone or with various concentrations of HMP (6.25-25 fjM) for 18 hrs and amount of IL-lpand TNF-a in culture supernatant was quantitated in culture supernatant by ELISA.

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