Dietary (n-3) Polyunsaturated Fatty Acids Affect the Kinetics of Pro- and Antiinflammatory Responses in Mice with Pseudomonas aeruginosa Lung Infection

Abstract

The underlying mechanisms by which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect host resistance to Pseudomonas aeruginosa are unclear. The aim of this study was to determine their role on the kinetic of pro- and antiinflammatory response in lung infection. Mice fed either a control diet or a diet enriched with EPA and DHA were infected intratracheally and we studied lung expression of proinflammatory markers [CXCL1, interleukin (IL)-6, tumor necrosis factor-alpha], antiinflammatory markers (IL-10, A20, and IkappaB alpha), and PPARalpha and PPARgamma. The inflammatory response was assessed using recruitment of neutrophils and macrophages into bronchoalveolar lavage fluid, bacterial clearance from the lung, pulmonary injury, and 7-d survival rate. Compared with the control group, EPA and DHA delayed the expression of proinflammatory markers during the first 2 h (P < 0.05), upregulated proinflammatory marker expression (P < 0.05), and induced overexpression of antiinflammatory markers at 8 h (P < 0.05), enhanced recruitment of neutrophils at 16 h (P < 0.05), and induced PPARalpha and PPARgamma overexpression at 4 and 8 h (P < 0.01), respectively. Pulmonary bacterial load decreased and pulmonary injury and mortality were reduced during the first 24 h (P < 0.05). In conclusion, EPA and DHA modulate the balance between pro- and antiinflammatory cytokines, alter the early response of the host to P. aeruginosa infection, and affect the early outcome of infection.

Docosapentaenoic acid monoacylglyceride reduces inflammation and vascular remodeling in experimental pulmonary hypertension

“…In addition, EPA and DHA have been shown to trigger anti-inflammatory effects by 1) inhibiting the metabolism of membrane AA to proinflammatory mediators, 2) producing anti-inflammatory and proresolving (resolvins and protectins) molecules, and 3) blocking the synthesis of proinflammatory enzymes and cytokines by interfering with NF-B pathways (35). n-3 PUFA and their derivatives also display beneficial effects in animal models of asthma (2,34) and cystic fibrosis (54). Indeed, in recent studies, we have demonstrated that n-3 PUFA monoacylglycerides such as MAG-DHA and MAG-EPA display anti-inflammatory effects in animal models of asthma.…”

Innate Immune Responses to Systemic Acinetobacter baumannii Infection in Mice: Neutrophils, but Not Interleukin-17, Mediate Host Resistance

“…IL-17 is known to be responsible for induction of downstream chemokines, such as KC/CXCL1, which are chemotactic for neutrophils (58). The induction of KC/ CXCL1 following infection has been documented for a wide variety of pathogens, including bacterial infections such as Pseudomonas aeruginosa (45,51,56), Chlamydia muridarum (63), Citrobacter rodentium (50,55), Listeria monocytogenes (53), Streptococcus pneumoniae (48,54), Leptospira interrogans (8), and Borrelia burgdorferi (3). In the present studies, KC/ CXCL1 induction was evaluated following systemic A. baumannii infection in C3HeB/FeJ mice.…”

Expression of the nuclear factor-κB inhibitor A20 is altered in the cystic fibrosis epithelium

“…GON et al [17] showed that A20 is essential in terminating TLR-2 and TLR-4 mediated interleukin (IL)-8 release from primary airway epithelial cells, while TIESSET et al [18] found A20 to be rapidly inducible in the lungs of healthy mice challenged with Pseudomonas aeruginosa. However, to our knowledge, A20 has not been investigated in chronic airways diseases, such as cystic fibrosis (CF) [19].…”