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Frontiers in Cellular and Infection... 2024Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here...
Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: -10--15-octadecadienoic acid (t10,c15-18:2) and -9--15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation.
Topics: Animals; Mice; Vascular Endothelial Growth Factor A; Fatty Acids, Omega-3; Down-Regulation; Disease Models, Animal; Dermatitis, Contact; Dinitrofluorobenzene; Skin; Keratinocytes; Female; Dermatitis, Allergic Contact; Humans; Gastrointestinal Microbiome; Feces
PubMed: 38841110
DOI: 10.3389/fcimb.2024.1355679 -
PloS One 2015Inflammatory bowel disease is a chronic gastrointestinal inflammatory disorder associated with changes in neuropeptide expression and function, including vasoactive...
Inflammatory bowel disease is a chronic gastrointestinal inflammatory disorder associated with changes in neuropeptide expression and function, including vasoactive intestinal peptide (VIP). VIP regulates intestinal vasomotor and secretomotor function and motility; however, VIP's role in development and maintenance of colonic epithelial barrier homeostasis is unclear. Using VIP deficient (VIPKO) mice, we investigated VIP's role in epithelial barrier homeostasis, and susceptibility to colitis. Colonic crypt morphology and epithelial barrier homeostasis were assessed in wildtype (WT) and VIPKO mice, at baseline. Colitic responses were evaluated following dinitrobenzene sulfonic acid (DNBS) or dextran-sodium sulfate (DSS) exposure. Mice were also treated with exogenous VIP. At baseline, VIPKO mice exhibited distorted colonic crypts, defects in epithelial cell proliferation and migration, increased apoptosis, and altered permeability. VIPKO mice also displayed reduced goblet cell numbers, and reduced expression of secreted goblet cell factors mucin 2 and trefoil factor 3. These changes were associated with reduced expression of caudal type homeobox 2 (Cdx2), a master regulator of intestinal function and homeostasis. DNBS and DSS-induced colitis were more severe in VIPKO than WT mice. VIP treatment rescued the phenotype, protecting VIPKO mice against DSS colitis, with results comparable to WT mice. In conclusion, VIP plays a crucial role in the development and maintenance of colonic epithelial barrier integrity under physiological conditions and promotes epithelial repair and homeostasis during colitis.
Topics: Animals; CDX2 Transcription Factor; Cell Count; Colitis; Dinitrofluorobenzene; Disease Susceptibility; Epithelial Cells; Goblet Cells; Homeodomain Proteins; Homeostasis; Intestines; Male; Mice, Inbred C57BL; Mice, Knockout; Protective Agents; Real-Time Polymerase Chain Reaction; Signal Transduction; Transcription Factors; Vasoactive Intestinal Peptide
PubMed: 25932952
DOI: 10.1371/journal.pone.0125225 -
PloS One 2017This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human...
This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human IBD. At a concentration of 4 g/kg/day, the goat whey improved the symptoms of intestinal inflammation, namely by decreasing the disease activity index, colonic weight/length, and leukocyte infiltration. Moreover, goat whey inhibited NF-κB p65 and p38 MAPK signaling pathways and consequently down-regulated the gene expression of various proinflammatory markers such as IL-1β, IL-6, IL-17, TNF-α, iNOS, MMP-9, ICAM-1. Also, goat whey increased the expression of proteins such as mucins, occludin proteins and cytokine signalling suppressors. The immunomodulatory properties of goat whey were also evaluated in vitro using the murine macrophage cell line Raw 264 and CMT-93 cells derived from mouse rectum carcinomas. The results revealed the ability of goat whey to inhibit the production of NO and reduce IL-6 production in LPS-stimulated cells. In conclusion, goat whey exhibited anti-inflammatory effects in the DNBS model of intestinal inflammation, and these observations were confirmed by its immunomodulatory properties in vitro. Together, our results indicate that goat whey could have applications for the treatment of IBD.
Topics: Animals; Anti-Inflammatory Agents; Colitis; Cytokines; Dinitrofluorobenzene; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Gene Expression Regulation; Goats; Inflammation Mediators; Intestinal Mucosa; Intestines; Male; Mice; RAW 264.7 Cells; Real-Time Polymerase Chain Reaction; Whey
PubMed: 28957373
DOI: 10.1371/journal.pone.0185382 -
Immunology Jan 2015Upon antigen/allergen recognition, epidermal Langerhans' cells (LC) are mobilized and migrate to the local lymph node where they play a major role in initiating or...
Upon antigen/allergen recognition, epidermal Langerhans' cells (LC) are mobilized and migrate to the local lymph node where they play a major role in initiating or regulating immune responses. It had been proposed that all chemical allergens induce LC migration via common cytokine signals delivered by TNF-α and IL-1β. Here the dependence of LC migration on TNF-α following treatment of mice with various chemical allergens has been investigated. It was found that under standard conditions the allergens oxazolone, paraphenylene diamine, and trimellitic anhydride, in addition to the skin irritant sodium lauryl sulfate, were unable to trigger LC mobilization in the absence of TNF-α signalling. In contrast, two members of the dinitrohalobenezene family (2,4-dinitrochlorobenzene [DNCB] and 2,4-dinitrofluorobenzene [DNFB]) promoted LC migration independently of TNF-R2 (the sole TNF-α receptor expressed by LC) and TNF-α although the presence of IL-1β was still required. However, increasing doses of oxazolone overcame the requirement of TNF-α for LC mobilization, whereas lower doses of DNCB were still able to induce LC migration in a TNF-α-independent manner. These novel findings demonstrate unexpected heterogeneity among chemical allergens and furthermore that LC can be induced to migrate from the epidermis via different mechanisms that are either dependent or independent of TNF-α. Although the exact mechanisms with regard to the signals that activate LC have yet to be elucidated, these differences may translate into functional speciation that will likely impact on the extent and quality of allergic sensitization.
Topics: Adjuvants, Immunologic; Allergens; Animals; Cell Movement; Dinitrofluorobenzene; Epidermis; Hypersensitivity; Immunization; Langerhans Cells; Mice; Mice, Inbred BALB C; Mice, Knockout; Oxazolone; Receptors, Tumor Necrosis Factor, Type II; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 25039377
DOI: 10.1111/imm.12359 -
Cellular Physiology and Biochemistry :... 2015Pruritus, also known as itch, is a common, unpleasant sensation that can be difficult to treat. Frequently, chronic itch is associated with the development of...
BACKGROUND/AIMS
Pruritus, also known as itch, is a common, unpleasant sensation that can be difficult to treat. Frequently, chronic itch is associated with the development of neuropathic pain resulting from nerve injury or insult. Previous studies have shown the involvement of spinal microglia in the development of neuropathic pain, but their role in chronic pruritus is unclear.
METHODS
For this study, we constructed a model of chronic pruritus in mice using repeated applications of 2, 4-dinitrofluorobenzene (DNFB) and showed prolonged scratching behavior in treated mice that continued for at least 7 d after the final DNFB treatment.
RESULTS
Scratching was accompanied by activation of spinal microglia and both were reduced by an inhibitor of microglial activity. We also showed that microglial activation entailed increased signaling in the p38 MAPK pathway, and treatment with a p38 inhibitor reduced scratching in DNFB-treated mice. We also examined the role of fractalkine/CX3CR1 signaling in the development of DNFB-induced pruritus and showed that intrathecal administration of antiserum against either CX3CR1or FKN inhibited p38 activity and decreased scratching.
CONCLUSION
Our results suggest that microglia are involved in pruritus induced by DNFB via FKN/CX3CR1/p38MAPK pathways similar to those participating in the development of neuropathic pain.
Topics: Animals; CX3C Chemokine Receptor 1; Dinitrofluorobenzene; Disease Models, Animal; Humans; Male; Mice; Microglia; Neuralgia; Pruritus; Receptors, Chemokine; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 25661672
DOI: 10.1159/000373929 -
International Journal of Molecular... Oct 2020CX3CL1 can function as both an adhesion molecule and a chemokine for CX3CR1 cells, such as T cells, monocytes, and NK cells. Recent studies have demonstrated that...
CX3CL1 can function as both an adhesion molecule and a chemokine for CX3CR1 cells, such as T cells, monocytes, and NK cells. Recent studies have demonstrated that CX3CL1-CX3CR1 interaction is associated with the development of various inflammatory skin diseases. In this study, we examined CX3CR1 involvement in 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity using CX3CR1 mice. Ear swelling and dermal edema were attenuated after DNFB challenge in CX3CR1 mice. Expression of TNF-α, IL-6, and M1 macrophage markers was decreased in the ears of CX3CR1 mice, whereas expression of M2 macrophage markers including arginase-1 was increased. Decreased TNF-α and IL-6 expression and increased arginase-1 expression were found in peritoneal macrophages from CX3CR1 mice. Furthermore, ear swelling was attenuated by depleting dermal macrophages in wild-type mice to a similar level to CX3CR1 mice. These results suggest that CX3CR1 deficiency could induce skewed polarization towards M2 phenotype in macrophages, resulting in attenuation of contact hypersensitivity response.
Topics: Animals; Biomarkers; CX3C Chemokine Receptor 1; Dermatitis, Contact; Dinitrofluorobenzene; Disease Models, Animal; Disease Susceptibility; Immunohistochemistry; Macrophage Activation; Macrophages; Mice; Mice, Knockout; Neutrophil Infiltration
PubMed: 33036460
DOI: 10.3390/ijms21197401 -
Immunology Jan 1985Irradiated C57BL/6 (B6) and C3H mice were reconstituted with bone marrow cells from BALB/c mice. The chimaeric mice, [BALB/c----B6] and [BALB/c----C3H], developed and...
Irradiated C57BL/6 (B6) and C3H mice were reconstituted with bone marrow cells from BALB/c mice. The chimaeric mice, [BALB/c----B6] and [BALB/c----C3H], developed and expressed contact sensitivity to DNFB. The in vivo responses paralleled to proliferative responses of regional lymph node cells of the chimaeras to DNBS in vitro. Furthermore, intravenous administration of DNBS rendered the chimaeras tolerant to subsequent sensitization with DNFB. The tolerance was transferred to lightly irradiated BALB/c mice by the spleen and lymph node T cells. These results represent marked contrast to our previous observations that [B6----C3H] and [B6----AKR] chimaeras were unable to develop specific unresponsiveness to stimulation with DNFB by the intravenous route. The controversial observations seen in the chimaeras prepared by BALB/c bone marrows and those prepared by B6 cells are discussed.
Topics: Animals; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Dermatitis, Contact; Dinitrofluorobenzene; Female; Immune Tolerance; Immunization, Passive; Lymph Nodes; Mice; Mice, Inbred Strains; Radiation Chimera; Spleen; T-Lymphocytes, Regulatory
PubMed: 3156086
DOI: No ID Found -
Evidence-based Complementary and... 2013Rhus verniciflua Stokes (RV) has traditionally been used as a food supplement and a traditional herbal medicine for centuries in Korea. Recent studies suggest that RV...
Rhus verniciflua Stokes (RV) has traditionally been used as a food supplement and a traditional herbal medicine for centuries in Korea. Recent studies suggest that RV has potent antioxidative, antitumor, and anti-inflammatory properties. In this study, the anti-inflammatory effects of RV from mice sensitized with 2,4-dinitrofluorobenzene (DNFB) and activated macrophages were investigated. The results showed that RV reduced ear swelling and hyperplasia of ear tissue as well as an increase in vascular permeability, which are characteristics of allergic contact dermatitis (ACD) with evident histomorphological changes in epidermis and dermis. Decreased numbers of infiltrated mast cells were seen in RV extract treated group, using toluidine blue staining. RV extract significantly regulates the expression of inducible nitric oxide synthase (iNOS) at the translational level in activated macrophages. Furthermore, RV extract and its active compound, fisetin, attenuated the level of tumor necrosis factor- α (TNF- α ) and interleukin 6 (IL-6) mRNA in LPS-stimulated macrophages. Anti-ACD effect of RV extract may be due to the suppression of iNOS and proinflammatory cytokines which might be mediated via the NF κ B signaling pathways. Collectively, RV extract has potential for alleviating ACD-like symptoms induced by DNFB in the mouse.
PubMed: 23710240
DOI: 10.1155/2013/879696 -
Journal of Dermatological Science Nov 2012Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC...
BACKGROUND
Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs).
OBJECTIVE
The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development.
METHODS
ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleen and skin draining lymph nodes were collected for immune staining.
RESULTS
TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4(+) and CD8(+) T cells, Foxp3(+)CD4(+) regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice.
CONCLUSION
Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases.
Topics: Animals; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Forkhead Transcription Factors; Histone Deacetylase Inhibitors; Hydroxamic Acids; Langerhans Cells; Mice; Mice, Inbred C57BL; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes
PubMed: 22999682
DOI: 10.1016/j.jdermsci.2012.09.001 -
The Journal of Neuroscience : the... Sep 2013Sickness behaviors, such as fatigue, mood alterations, and cognitive dysfunction, which result from changes in central neurotransmission, are prevalent in systemic...
Sickness behaviors, such as fatigue, mood alterations, and cognitive dysfunction, which result from changes in central neurotransmission, are prevalent in systemic inflammatory diseases and greatly impact patient quality of life. Although, microglia (resident cerebral immune cells) and cytokines (e.g., TNFα) are associated with changes in central neurotransmission, the link between peripheral organ inflammation, circulating cytokine signaling, and microglial activation remains poorly understood. Here we demonstrate, using cerebral intravital microscopy, that in response to liver inflammation, there is increased monocyte specific rolling and adhesion along cerebral endothelial cells (CECs). Peripheral TNFα-TNFR1 signaling and the adhesion molecule P-selectin are central mediators of these monocyte-CEC adhesive interactions which were found to be closely associated with microglial activation, decreased central neural excitability and sickness behavior development. Similar monocyte-CEC adhesive interactions were also observed in another mouse model of peripheral organ inflammation (i.e., 2,4-dinitrobenzene sulfonic acid-induced colitis). Our observations provide a clear link between peripheral organ inflammation and cerebral changes that impact behavior, which can potentially allow for novel therapeutic interventions in patients with systemic inflammatory diseases.
Topics: Alanine Transaminase; Animals; Cell Adhesion; Cerebral Cortex; Cholestasis; Colitis; Cytokines; Dinitrofluorobenzene; Disease Models, Animal; Endothelial Cells; Female; Hippocampus; Illness Behavior; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monocytes; Muramidase; P-Selectin; Pentylenetetrazole
PubMed: 24027287
DOI: 10.1523/JNEUROSCI.1329-13.2013