Modulation of Lipopolysaccharide-Stimulated Macrophage Tumor Necrosis Factor-α Production by ω-3 Fatty Acid Is Associated with Differential Cyclooxygenase-2 Protein Expression and Is Independent of Interleukin-10

Babcock, Tricia A.; Novak, Todd E.; Ong, Evan; Jho, David H.; Helton, W. Scott; Espat, N. Joseph

doi:10.1006/jsre.2002.6498

Cited by 44 publications

(22 citation statements)

References 17 publications

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“…Such effects could arise from changes induced directly in the macrophages themselves, possibly via Toll-like receptors. [30][31][32] In addition, indirect effects may operate from the transfer of the fat and glycogen from macrophages to lymphocytes, as small lymphocytes, in comparison with macrophages, directly acquire comparatively low levels of fat and glycogen. 29 Pre-adipocytes are reported to have properties of macrophages, 33,34 and cells from adipose tissue can transdifferentiate into macrophages in vivo.…”

Section: Discussionmentioning

confidence: 99%

Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

Maroof¹,

English²,

Bedford³

et al. 2005

Immunology

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SummaryOn maturation, dendritic cells (DCs) become highly active cells equipped for antigen uptake, migration and clustering and activation of T cells. We therefore asked whether DCs acquire fat and glycogen stores as they mature. DCs were generated from mouse bone marrow stem cells by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 7-8 days. Stimulation of the DCs with lipopolysaccharide (LPS) for the last 24 hr of culture, or exposure to 1-15 ng/ml of interleukin (IL)-4 during development, resulted in production of DCs not only with an increased ability to stimulate T cells but also with an increasingly lacy appearance on transmission electron microscopy, with multiple unstained areas in the cytoplasm. This changed morphology was associated with the presence of increasing amounts of fat and glycogen, identified by Sudan Black and periodic acid leukofushin/Schiff (PAS) staining, respectively. Lacy DCs up-regulated type 1 and type 2 scavenger receptors, providing possible mechanisms contributing to these changes. Lacy DCs were found occasionally amongst freshly isolated splenic and lymph node DCs. DCs can be isolated from human adipose tissue, and we tested whether lacy DCs acquiring fat and glycogen were present in mouse omentum. CD45 + cells migrating from the omentum expressed specific DC markers CD11c and 33D1, costimulatory molecules and major histocompatibility complex (MHC) class II, and most showed darkly staining fat inclusions. Thus, during development, DCs can acquire large amounts of fat and glycogen, accumulation of which is promoted by antigen exposure and modulated by the cytokine milieu and location, and which may act as a link between energy stores and immune function.

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Section: Discussionmentioning

confidence: 99%

Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

Maroof¹,

English²,

Bedford³

et al. 2005

Immunology

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“…Inflammatory cytokines. Cell-culture studies have demonstrated that EPA and DHA can inhibit the production of IL-1b and TNFa by monocytes (64) and the production of IL-6 and IL-8 by venous endothelial cells (65,66) . Fish oil feeding decreases ex vivo production of TNFa, IL-1b and IL-6 by rodent macrophages (67)(68)(69) .…”

Section: Inflammatory Mediator Productionmentioning

confidence: 99%

Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on ‘Nutrition and autoimmune disease’ PUFA, inflammatory processes and rheumatoid arthritis

Calder

2008

Proc. Nutr. Soc.

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease manifested by swollen and painful joints, bone erosion and functional impairment. The joint lesions are characterised by infiltration of T lymphocytes, macrophages and B lymphocytes into the synovium and by synovial inflammation involving eicosanoids, cytokines and matrix metalloproteinases. In relation to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid, which is the precursor of inflammatory eicosanoids such as PGE2 and leukotriene B4, and the n-3 PUFA EPA and DHA, which are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in RA, and the efficacy of non-steroidal anti-inflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA also gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. In addition to modifying the lipid mediator profile, n-3 PUFA exert effects on other aspects of immunity relevant to RA such as antigen presentation, T-cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits in patients with RA that include reducing pain, duration of morning stiffness and use of non-steroidal anti-inflammatory drugs.

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“…EPA does not activate NF-kB in a monocytic cell line (Camandola et al 1996), while both EPA and DHA inhibit endotoxinstimulated production of IL-6 and IL-8 by cultured human endothelial cells (de Caterina et al 1994;Khalfoun et al 1997). More recent studies have shown that: (1) EPA does not induce TNF-a, IL-1a or IL-1b (Priante et al 2002) or IL-6 (Bordin et al 2003) in osteoblasts, and even counters the up regulating effect of arachidonic acid (Priante et al 2002); (2) EPA and DHA can totally abolish cytokineinduced up-regulation of TNF-a, IL-1a and IL-1b in cultured bovine chondrocytes and in human osteoarthritic cartilage explants (Curtis et al 2000(Curtis et al , 2002; (3) EPA or fish oil inhibit endotoxin-induced TNF-a production by monocytes (Lo et al 1999;Babcock et al 2002; Zhao et al 2004). EPA is also less potent than arachidonic acid in inducing IL-6 expression by macrophages (Bagga et al 2003).…”

Section: Fish Oil Inflammation and Immunitymentioning

confidence: 99%

Use of fish oil in parenteral nutrition: rationale and reality

Calder

2006

Proc. Nutr. Soc.

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Excessive or inappropriate inflammation and immunosuppression are components of the response to surgery, trauma, injury and infection in some individuals and can lead, progressively, to sepsis and septic shock. The hyperinflammation is characterised by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids and other inflammatory mediators, while the immunosuppression is characterised by impairment of antigen presentation and of T-helper lymphocyte type-1 responses. Long-chain n-3 fatty acids from fish oil decrease the production of inflammatory cytokines and eicosanoids. They act both directly (by replacing arachidonic acid as an eicosanoid substrate and by inhibiting arachidonic acid metabolism) and indirectly (by altering the expression of inflammatory genes through effects on transcription factor activation). Thus, long-chain n-3 fatty acids are potentially useful anti-inflammatory agents and may be of benefit in patients at risk of hyperinflammation and sepsis. As a consequence, an emerging application for n-3 fatty acids, in which they may be added to parenteral (or enteral) formulas, is in surgical or critically-ill patients. Parenteral nutrition that includes n-3 fatty acids appears to preserve immune function better than standard formulas and appears to diminish the extent of the inflammatory response. Studies to date are suggestive of clinical benefits from these approaches, especially in patients post surgery, although evidence of clinical benefit in patients with sepsis is emerging.

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Modulation of Lipopolysaccharide-Stimulated Macrophage Tumor Necrosis Factor-α Production by ω-3 Fatty Acid Is Associated with Differential Cyclooxygenase-2 Protein Expression and Is Independent of Interleukin-10

Cited by 44 publications

References 17 publications

Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on ‘Nutrition and autoimmune disease’ PUFA, inflammatory processes and rheumatoid arthritis

Use of fish oil in parenteral nutrition: rationale and reality

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