Effect and mechanism of Prunella vulgaris L. extract on alleviating lipopolysaccharide-induced acute mastitis in protecting the blood-milk barrier and reducing inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: According to ancient literature, Prunella vulgaris L. (P vulgaris) alleviates mastitis and has been used in China for many years; however, there are no relevant reports that confirm this or the mechanism of its efficacy. AIM OF THE STUDY: To explore the anti-acute mastitis effect and potential mechanism of P vulgaris extract. MATERIALS AND METHODS: First, the active ingredients and targets of P vulgaris against mastitis were predicted using network pharmacology. Next, the relevant active ingredients were enriched using macroporous resins and verified using UV and UPLC-Q-TOF-MS/MS. Lastly, a mouse model of acute mastitis was established by injecting lipopolysaccharides into the mammary gland and administering P vulgaris extract by oral gavage. The pathological changes in mammary tissue were observed by HE staining. Serum and tissue inflammatory factors were measured by ELISA method. MPO activity in mammary tissue was measured using colorimetry and MPO expression was detected by immunohistochemistry. The expression of tight junction proteins (ZO-1, claudin-3, and occludin) in mammary tissue was detected by immunofluorescence and Western blot. iNOS and COX-2 in mammary tissue were detected by Western blot. MAPK pathway and NF-κB pathway related proteins were also detected by Western blot. RESULTS: Network pharmacology predicted that phenolic acids and flavonoids in P vulgaris had anti-mastitis effects. The contents of total flavonoids and total phenolic acids in P vulgaris extract were 64.5% and 29.4%, respectively. UPLC-Q-TOF-MS/MS confirmed that P vulgaris extract contained phenolic acids and flavonoids. The results of animal experiments showed that P vulgaris extract reduced lipopolysaccharide-induced inflammatory edema, inflammatory cell infiltration, and interstitial congestion of mammary tissue. It also reduced the levels of serum and tissue inflammatory factors TNF-α, IL-6, and IL-1ß, and inhibited the activation of MPO. Furthermore, it downregulated the expression of MAPK and NF-κB pathway-related proteins. The expressions of ZO-1, occludin, and claudin-3 in mammary gland tissues were upregulated. CONCLUSIONS: P vulgaris extract can maintain the integrity of mammary connective tissue and reduce its inflammatory response to prevent acute mastitis. Its mechanism probably involves regulating NF-κB and MAPK pathways.

Wogonin attenuates inflammation and oxidative stress in lipopolysaccharide-induced mastitis by inhibiting Akt/NF-κB pathway and activating the Nrf2/HO-1 signaling.

Mastitis is a disease involved in inflammation of breast which affects human and animals. Wogonin is one bioactive compound from many Chinese herbal medicines, which have multiple properties, including anti-inflammatory activity. However, the roles of wogonin in mastitis progression are largely undefined. Mastitis models were established using LPS-treated mice and mammary epithelial cells (MECs). Infiltration of inflammatory cells was analyzed by hematoxylin-eosin staining and myeloperoxidase (MPO) activity. Inflammatory cytokine (TNF-α and IL-1ß) levels were detected via ELISA. The phosphorylation and total of Akt and NF-κB levels and content of Nrf2 and HO-1 were measured via western blot. Cell viability was examined by CCK-8 assay. Oxidative stress was assessed by ROS generation and levels of MDA, GSH, and SOD. Wogonin attenuated LPS-induced infiltration of inflammatory cells, increase of MPO activity and levels of TNF-α and IL-1ß, and activation of the Akt/NF-κB pathway in murine mammary gland tissues, and promoted activation of Nrf2/HO-1 signaling. Wogonin did not affect MEC viability, but mitigated LPS-induced inflammation in MECs by reducing TNF-α and IL-1ß levels. Wogonin relieved LPS-induced oxidative stress in MECs through decreasing ROS generation and MDA level and increasing GSH and SOD levels. Wogonin repressed LPS-induced activation of the Akt/NF-κB pathway in MECs and increased Nrf2/HO-1 signaling activation. Activated Akt/NF-κB signaling or Nrf2/HO-1 signaling inactivation reversed the suppressive effects of wogonin on LPS-induced inflammation and oxidative stress in MECs. Wogonin mitigates LPS-induced inflammation and oxidative stress of MECs via suppressing activation of the Akt/NF-κB signaling and activating Nrf2/HO-1 pathway, indicating the therapeutic potential of wogonin in mastitis.

Selenium and Taurine Combination Is Better Than Alone in Protecting Lipopolysaccharide-Induced Mammary Inflammatory Lesions via Activating PI3K/Akt/mTOR Signaling Pathway by Scavenging Intracellular ROS.

Mastitis is mainly induced by gram-negative bacterial infections, causing devastating economic losses to the global cattle industry. Both selenium (Se) and taurine (Tau) exhibit multiple biological effects, including reducing inflammation. However, no studies have reported the protective effect of the combined use of Se and Tau against mastitis, and the underlying mechanisms remain unclear. In this study, lipopolysaccharide (LPS), the vital virulence factor of gram-negative bacteria, was used to construct the in vivo and vitro mastitis models. The results of in vivo model showed that Se and Tau combination was more effective than either substance alone in reducing tissue hyperemia, edema, and neutrophil infiltration in the mammary acinar cavity, improving the blood-milk barrier in LPS-induced mice mastitis, and decreasing the expression of proinflammatory factors and the activity of MPO. Moreover, Se and Tau combination significantly increased the levels of LPS-induced reduction in PI3K/Akt/mTOR, but the expressions of TLRs and NLRP3 were not significantly changed in the mammary tissue. In the in vitro experiments, the effects of Se and Tau combination or alone on inflammatory factors, inflammatory mediators, MPO activity, and blood-milk barrier were consistent with those in vivo. The Se and Tau combination has also been found to increase the survival rate of BMECs compared with each substance alone via promoting cellular proliferation and inhibiting apoptosis. Also, it has been confirmed that this combination could restore the LPS-induced inhibition in the PI3K/Akt/mTOR signaling pathway. Inhibition of mTOR by Rapamycin counteracted the combined protection of SeMet and Tau against LPS-induced inflammatory damage, the inhibition of PI3K by LY294002 blocked the activation of mTOR, and the accumulation of ROS by the ROS agonist blocked the activation of PI3K. In conclusion, these findings suggested that Se and Tau combination was better than either substance alone in protecting LPS-induced mammary inflammatory lesions by upregulating the PI3K/Akt/mTOR signaling pathway.

Chitosan functionalized graphene oxide nanocomposites for fluorescence imaging of apoptotic processes and targeted anti-inflammation study.

This work reports novel chitosan functionalized graphene oxide (GO) nanocomposites combined fluorescence imaging and therapeutic functions in one agent, which can serve as a promising alternative to alleviate related diseases caused hyperinflammation. Briefly, GO was designed to be conjugated with chitosan, fluorescein-labeled peptide, toll-like receptor 4 antibody and hydroxycamptothecin/aloe emodin. We have demonstrated that such nanocomposites could effectively achieve active targeted delivery of pro-apoptotic and anti-inflammatory drugs into inflammatory cells and cause cells apoptosis by acid-responsive drug release. Moreover, confocal fluorescence imaging confirms that the drug-induced inflammatory cells apoptosis could be visualized the light-up fluorescence of fluorescein activated by caspase-3. Meanwhile, inflammatory-related biomarkers have down-regulated after the nanocomposites' treatment in both vitro and vivo experiments consistent with the results in histological sections. In summary, the bifunctional nanocomposites that possess anti-inflammation and fluorescence imaging could serve as a promising therapeutic agent for reducing hyperinflammation caused by numerous diseases.

Forsythiaside a plays an anti-inflammatory role in LPS-induced mastitis in a mouse model by modulating the MAPK and NF-κB signaling pathways.

Forsythiaside A, a major bioactive component extracted from Forsythiae fructus, possesses multiple biological properties, especially anti-inflammatory properties. In the present study, the anti-inflammatory effect of forsythiaside A was investigated in lipopolysaccharide (LPS)-induced acute mastitis in mice. Our results showed that the expression levels of IL-1ß, IL-6, TNF-α, p38 MAPK, IκBα, and NF-κB p65 in the LPS group were all up-regulated, and obvious pathological changes were observed by sectioning. Compared with those in the LPS group, the expression levels of the above factors were significantly reduced, and the inflammation symptoms were also significantly reduced by section observation after forsythiaside A intervention. These results indicated that forsythiaside A effectively inhibited LPS-induced mammary inflammation in mice by attenuating the activation of the NF-κB and p38 MAPK signaling pathways.

Rutin protects against lipopolysaccharide-induced mastitis by inhibiting the activation of the NF-κB signaling pathway and attenuating endoplasmic reticulum stress.

Rutin, found widely in traditional Chinese medicine materials, is used to treat eye swelling and pain, hypertension, and hyperlipidemia. In the present study, a mouse mastitis model induced by lipopolysaccharide (LPS) was established to explore rutin's inhibitory mechanism on mastitis via nuclear factor kappa B (NF-κB) inflammatory signaling and the relationship between NF-κB signaling and endoplasmic reticulum (ER) stress. Mice were divided into six groups: Control group, LPS model group, LPS + rutin (25, 50, and 100 mg/kg) and LPS + dexamethasone (DEX) group. DEX, rutin, and PBS (control and LPS groups) were administered 1 h before and 12 h after perfusion of LPS. After LPS stimulation for 24 h, to evaluate rutin's therapeutic effect on mastitis, the mammary tissues of each group were collected to detect histopathological injury, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 mRNA and protein levels; and glucose-regulated protein, 78 kDa (GRP78) protein levels. The protein and mRNA levels of TNF-α, IL-1ß, and IL-6 in the LPS + rutin group were significantly lower than those in the LPS model group. Similarly, p50/p105, phosphorylated (p)-p65/p65 and p-inhibitor of nuclear factor kappa b kinase subunit beta (p-IKKß)/IKKß ratios in the LPS + rutin group (50 mg/kg) and LPS + rutin group (100 mg/kg) decreased significantly. GRP78 protein expression was significantly higher in LPS + rutin group (100 mg/kg). The structure of mammary tissue became gradually more intact and vacuolization of acini decreased as the rutin concentration increased. The nuclear quantity of p65 in the LPS + rutin group decreased significantly in a rutin dose-dependent manner. Rutin had an anti-inflammatory effect in the LPS-induced mouse mastitis model, manifested by inhibition of NF-κB pathway activation and attenuation of ER stress.

Effect of Postnatal HIV Treatment on Clinical Mastitis and Breast Inflammation in HIV-Infected Breast-feeding Women.

BACKGROUND: The relationship between mastitis and antiretroviral therapy among HIV-positive, breast-feeding women is unclear. METHODS: In the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, conducted in Lilongwe, Malawi, 2369 mother-infant pairs were randomized to a nutritional supplement group and to one of three treatment groups: maternal antiretroviral therapy (ART), infant nevirapine (NVP) or standard of care for 24 weeks of exclusive breast-feeding and 4 weeks of weaning. Among 1472 HIV-infected women who delivered live infants between 2004 and 2007, we estimated cumulative incidence functions and sub-distribution hazard ratios (HR) of mastitis or breast inflammation comparing women in maternal ART (n = 487) or infant nevirapine (n = 492) groups to the standard of care (n = 493). Nutritional supplement groups (743 took, 729 did not) were also compared. RESULTS: Through 28-weeks post-partum, 102 of 1472 women experienced at least one occurrence of mastitis or breast inflammation. The 28-week risk was higher for maternal ART (risk difference (RD) 4.5, 95% confidence interval (CI) 0.9, 8.1) and infant NVP (RD 3.6, 95% CI 0.3, 6.9) compared to standard of care. The hazard of late-appearing mastitis or breast inflammation (from week 5-28) was also higher for maternal ART (HR 6.7, 95% CI 2.0, 22.6) and infant NVP (HR 5.1, 95% CI 1.5, 17. 5) compared to the standard of care. CONCLUSIONS: Mastitis or breast inflammation while breast-feeding is a possible side effect for women taking prophylactic ART and women whose infants take NVP, warranting additional research in the context of postnatal HIV transmission.

Puerarin Exerts an Antiinflammatory Effect by Inhibiting NF-kB and MAPK Activation in Staphylococcus aureus-Induced Mastitis.

Mastitis is defined as the inflammation of the mammary gland. There is generally no effective treatment for mastitis in animals. Puerarin, extracted from Radix puerariae, has been proven to possess many biological activities. The present study aims to reveal the potential mechanism that is responsible for the antiinflammatory action of puerarin in Staphylococcus aureus (S. aureus)-induced mastitis in mice. Histopathological changes showed that puerarin ameliorated the inflammatory injury induced by S. aureus. Quantitative real-time polymerase chain reaction and ELISA analysis indicated that puerarin not only suppressed the production of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 but also promoted the secretion of IL-10. Toll-like receptor 2 (TLR2) is important in the immune defense against S. aureus infection. Research in molecular biology has shown that the expression of TLR2 was inhibited with administration of puerarin. Further studies were performed on NF-kB and mitogen-activated protein kinase signaling pathways using western blot. The results demonstrated that puerarin suppressed phosphorylated IkBα, p65, p38, extracellular signal-regulated kinase 1and 2 (ERK), and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. All of the results suggested that puerarin may be a potential therapy for treating mastitis. Copyright © 2016 John Wiley & Sons, Ltd.

Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-κB and MAPK signaling pathways in LPS-induced mastitis in mice.

Baicalein is a phenolic flavonoid presented in the dry roots of Scutellaria baicalensis Georgi. It has been reported that baicalein possesses a number of biological properties, such as antiviral, antioxidative, anti-inflammatory, antithrombotic, and anticancer properties. However, the effect of baicalein on mastitis has not yet been reported. This research aims to detect the effect of baicalein on lipopolysaccharide (LPS)-induced mastitis in mice and to investigate the molecular mechanisms. Baicalein was administered intraperitoneally 1h before and 12h after LPS treatment. The results indicated that baicalein treatment markedly attenuated the damage of the mammary gland induced by LPS, suppressed the activity of myeloperoxidase (MPO) and the levels of tumor necrosis factor (TNF-α) and interleukin (IL-1ß) in mice with LPS-induced mastitis. Besides, baicalein blocked the expression of Toll-like receptor 4 (TLR4) and then suppressed the phosphorylation of nuclear transcription factor-kappaB (NF-κB) p65 and degradation inhibitor of NF-κBα (IκBα) and, and inhibited the phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signal pathway. These findings suggested that baicalein may have a potential prospect against mastitis.

Geniposide inhibited lipopolysaccharide-induced apoptosis by modulating TLR4 and apoptosis-related factors in mouse mammary glands.

AIMS: Geniposide, a major iridoid glycoside found in gardenia fruit, is widely used in Asian countries for its anti-inflammatory, anti-tumor and anti-apoptotic activities. Although the anti-inflammatory effect of geniposide has been widely reported, its anti-apoptotic role in mastitis remains unclear. In the present study, we investigated whether geniposide exerts anti-apoptotic activity in lipopolysaccharide (LPS)-induced mouse mammary glands. MAIN METHODS: We established a LPS-induced mouse mastitis model and LPS-stimulated primary mouse mammary epithelial cells (mMECs) model to investigate the anti-apoptotic effect of geniposide and the underlying mechanism of action. In the in vivo studies, apoptosis in mammary glands was detected by TUNEL. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expression of Bax, Bcl-2, Caspase-3 and p53. In the in vitro study, the apoptosis in mammary epithelial cells was measured by Live-Dead staining. Western blot and qRT-PCR analysis were used to analyze the expression of Bax, Bcl-2, Caspase-3, p53 and TLR4. KEY FINDINGS: Geniposide alleviated mammary gland apoptosis, down-regulated Bax expression, inhibited Caspase-3 cleavage and p53 phosphorylation and up-regulated Bcl-2 expression in vivo. In vitro, geniposide decreased the ratio of dead cells in a dose-dependent manner. Geniposide inhibited Bax expression and Caspase-3 cleavage, and up-regulated the expression of Bcl-2. Moreover, geniposide down-regulated the expression of TLR4 and repressed the phosphorylation of p53. SIGNIFICANCE: These results demonstrate that the anti-apoptotic property of geniposide is due to its modulation of TLR4 and apoptosis-related factors (p53, Bax, Bcl-2 and Caspase-3) in LPS-induced mouse mastitis.

Low-level laser therapy attenuates LPS-induced rats mastitis by inhibiting polymorphonuclear neutrophil adhesion.

The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on a rat model of lipopolysaccharide (LPS)-induced mastitis and its underlying molecular mechanisms. The rat model of mastitis was induced by inoculation of LPS through the canals of the mammary gland. The results showed that LPS-induced secretion of IL-1ß and IL-8 significantly decreased after LLLT (650 nm, 2.5 mW, 30 mW/cm(2)). LLLT also inhibited intercellular adhesion molecule-1 (ICAM-1) expression and attenuated the LPS-induced decrease of the expression of CD62L and increase of the expression of CD11b. Moreover, LLLT also suppressed LPS-induced polymorphonuclear neutrophils (PMNs) entering the alveoli of the mammary gland. The number of PMNs in the mammary alveolus and the myeloperoxidase (MPO) activity were decreased after LLLT. These results suggested that LLLT therapy is beneficial in decreasing the somatic cell count and improving milk nutritional quality in cows with an intramammary infection.

Inhibitory effects of astragalin on lipopolysaccharide-induced inflammatory response in mouse mammary epithelial cells.

BACKGROUND: Tea brewed from the leaves of persimmon or Rosa agrestis have several medical functions including treating allergy, antiatopic dermatitis, and anti-inflammatory effects. The objective of this study was to investigate the molecular mechanisms of astragalin, a main flavonoid component isolated from these herbs, in modifying lipopolysaccharide (LPS)-induced signaling pathways in primary cultured mouse mammary epithelial cells (mMECs). MATERIALS AND METHODS: The mMECs were treated with LPS in the absence or presence of different concentrations of astragalin. The expression of proinflammatory cytokines tumor necrosis factor α, and interleukin 6, as well as nitric oxide production were determined by enzyme-linked immunosorbent assay and Griess reaction, respectively. Cyclooxygenase-2, inducible nitric oxide synthase, toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), inhibitor protein of NF-κB (IκBα), P38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase were measured by Western blot. RESULTS: The results showed that astragalin suppressed the expression of tumor necrosis factor α, interleukin 6, and nitric oxide in a dose-dependent manner in mMECs. Western blot results showed that the expression of inducible nitric oxide synthase and cyclooxygenase-2 was inhibited by astragalin. Besides, astragalin efficiently decreased LPS-induced TLR4 expression, NF-κB activation, IκBα degradation, and the phosphorylation of p38, extracellular signal-regulated kinase in BMECs. CONCLUSIONS: Our results indicated that astragalin exerts anti-inflammatory properties possibly via the inactivation of TLR4-mediated NF-κB and mitogen-activated protein kinases signaling pathways in LPS-stimulated mMECs. Thus, astragalin may be a potential therapeutic agent for bovine mastitis.

Patchouli alcohol dampens lipopolysaccharide induced mastitis in mice.

Patchouli alcohol (PA), a tricyclic sesquiterpene isolated from Pogostemonis Herba, has been known to exhibit antioxidant, anti-inflammatory, and other important therapeutic activities. The aim of this study was to investigate the effects of PA on LPS-induced mastitis in vivo and the possible mechanism. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Mice were pretreated with dexamethasone or PA 1 h before and 12 h after induction of LPS. The myeloperoxidase activity and inflammatory cytokines production in mammary tissues were determined. The effects of PA on NF-κB signal pathways were analyzed by Western blotting. The results showed that PA inhibited the LPS-induced TNF-α, IL-6, and IL-1ß production in a dose manner. It was also observed that PA attenuated mammary histopathologic changes. Furthermore, Western blot analysis showed that PA could inhibit the phosphorylation of NF-κB and IκB induced by LPS. These results indicate that PA inhibits NF-κB signaling pathways to attenuate inflammatory injury induced by LPS. PA may be a potent therapeutic reagent for the prevention of mastitis.

Dietary selenium deficiency exacerbates lipopolysaccharide-induced inflammatory response in mouse mastitis models.

Selenium (Se) is an essential micronutrient that plays a critical role in anti-inflammatory processes and antioxidant defense system. In this study, we investigated the effects of dietary selenium deficiency on lipopolysaccharide (LPS)-induced mastitis in mouse models. Se content in the liver was assessed by fluorescent atomic absorption spectrometry. Glutathione peroxidase (GPx) activity in the blood, myeloperoxidase (MPO) activity, tumor necrosis actor alpha (TNF-α), and interleukin (IL)-1ß in the supernatant of the mammary tissue were determined according to the corresponding kits. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions were evaluated by Western blotting. The results showed that the Se-deficient mouse model was successfully replicated, and selenium deficiency exacerbated mammary gland histopathology, increased the expressions of TNF-α and IL-1ß, and facilitated the activation of iNOS and COX-2 in LPS-induced mouse mastitis. In conclusion, our studies demonstrated that selenium deficiency resulted in more severe inflammatory response in LPS-induced mouse mastitis.

Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice.

Kaempferol isolated from the root of Zingiberaceae plants galangal and other Chinese herbal medicines have been reported to have anti-inflammatory properties. However, the anti-inflammatory effects of kaempferol on lipopolysaccharide (LPS)-induced mastitis are unknown and their underlying molecular mechanisms remain to be explored. The aim of this study was to evaluate the effects of kaempferol on LPS-induced mouse mastitis. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Kaempferol was injected 1 h before and 12 h after induction of LPS intraperitoneally. The present results showed that kaempferol markedly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in a dose-dependent manner, which were increased in LPS-induced mouse mastitis. Furthermore, kaempferol suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 subunit and the degradation of its inhibitor IκBα. All results suggest that anti-inflammatory effects of kaempferol against the LPS-induced mastitis possibly through inhibition of the NF-κB signaling pathway. Kaempferol may be a potential therapeutic agent for mastitis.

Mammary inflammation around parturition appeared to be attenuated by consumption of fish oil rich in n-3 polyunsaturated fatty acids.

BACKGROUND: Mastitis endangers the health of domestic animals and humans, and may cause problems concerning food safety. It is documented that n-3 polyunsaturated fatty acids (PUFA) play significant roles in attenuating saturated fatty acids (SFA)-induced inflammation. This study was therefore conducted to determine whether mammary inflammation could be affected by consumption of diets rich in n-3 PUFA. METHODS: Forty-eight rats after mating began to receive diets supplemented with 5% fish oil (FO) or 7% soybean oil (SO). Blood and mammary tissue samples (n = 6) at day 0 and 14 of gestation and day 3 postpartum were collected 9 hours after intramammary infusion of saline or lipopolysaccharide (LPS) to determine free fatty acids (FFA) concentration and FA composition in plasma and inflammation mediators in mammary tissues. RESULTS: At day 14 of gestation and day 3 postpartum, the FO-fed rats had lower plasma concentrations of C18:2n6, C20:4n6, total n-6 PUFA and SFA, and higher plasma concentrations of C20:5n3 and total n-3 PUFA than the SO-fed rats. Plasma C22:6n3 concentration was also higher in the FO-fed than in the SO-fed rats at day 3 postpartum. Compared with the SO-fed rats, the FO-fed rats had lower mammary mRNA abundance of xanthine oxidoreductase (XOR) and protein level of tumor necrosis factor (TNF)-α, but had higher mammary mRNA abundances of interleukin (IL)-10 and peroxisome proliferator-activated receptor (PPAR)-γ at day 14 of gestation. Following LPS infusion at day 3 postpartum, the SO-fed rats had increased plasma concentrations of FFA, C18:1n9, C18:3n3, C18:2n6 and total n-6 PUFA, higher mammary mRNA abundances of IL-1ß, TNF-α and XOR but lower mammary mRNA abundance of IL-10 than the FO-fed rats. CONCLUSIONS: Mammary inflammation around parturition appeared to be attenuated by consumption of a diet rich in n-3 PUFA, which was associated with up-regulated expression of IL-10 and PPAR-γ.