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Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway.

Badshah H, Ali T, Kim MO - Sci Rep (2016)

Bottom Line: Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1.Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3.Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.

ABSTRACT
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

No MeSH data available.


Related in: MedlinePlus

Osmotin inhibits LPS-induced COX-2, iNOS, TNF-α and IL-1β expression (A) Shown are representative western blots probed with antibodies of COX-2, iNOS, TNF-α and IL-1β in the hippocampus of adult mice. The protein bands were quantified using sigma gel software. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Showed are representative photomicrographs of immunofluorescence analysis of Tnfα positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing DG, CA1 and CA3 region of hippocampus showed TNF-α stained brain tissue at magnification 10× objective field, scale bar= 100 µm. Symbols for treatment groups and level of significance are mentioned in data analysis section of material methods.
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f3: Osmotin inhibits LPS-induced COX-2, iNOS, TNF-α and IL-1β expression (A) Shown are representative western blots probed with antibodies of COX-2, iNOS, TNF-α and IL-1β in the hippocampus of adult mice. The protein bands were quantified using sigma gel software. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Showed are representative photomicrographs of immunofluorescence analysis of Tnfα positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing DG, CA1 and CA3 region of hippocampus showed TNF-α stained brain tissue at magnification 10× objective field, scale bar= 100 µm. Symbols for treatment groups and level of significance are mentioned in data analysis section of material methods.

Mentions: NFκB activation is the primary event in the progression of the proinflammatory signaling pathway. LPS administration induced iNOS activation and the release of proinflammatory mediators, such as TNF-α and IL-1β, via the NFκB–MAPK pathway27. Font-Nieves et al.3 demonstrated that COX-2 activation followed an NFκB-dependent pathway in LPS-treated samples3. Hippocampal protein expression levels of COX-2, iNOS, TNF-α, and IL-1β were evaluated to examine the effects of LPS and osmotin on the release of inflammatory mediators. Our results demonstrated that LPS treatment for the indicated period induced a higher level of protein expression compared to the vehicle-treated group, and osmotin administration decreased the protein levels of these inflammatory markers in the hippocampus of LPS-injected mice (Fig. 3A). Immunofluorescence detection of TNF-α revealed that osmotin effectively attenuated LPS-induced increases of TNF-α levels in the DG, CA1, and CA3 regions of the hippocampus (Fig. 3B).


Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway.

Badshah H, Ali T, Kim MO - Sci Rep (2016)

Osmotin inhibits LPS-induced COX-2, iNOS, TNF-α and IL-1β expression (A) Shown are representative western blots probed with antibodies of COX-2, iNOS, TNF-α and IL-1β in the hippocampus of adult mice. The protein bands were quantified using sigma gel software. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Showed are representative photomicrographs of immunofluorescence analysis of Tnfα positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing DG, CA1 and CA3 region of hippocampus showed TNF-α stained brain tissue at magnification 10× objective field, scale bar= 100 µm. Symbols for treatment groups and level of significance are mentioned in data analysis section of material methods.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837357&req=5

f3: Osmotin inhibits LPS-induced COX-2, iNOS, TNF-α and IL-1β expression (A) Shown are representative western blots probed with antibodies of COX-2, iNOS, TNF-α and IL-1β in the hippocampus of adult mice. The protein bands were quantified using sigma gel software. The density values are expressed in arbitrary units as the mean ± SEM for the indicated proteins (n = 5 animals per group). (B) Showed are representative photomicrographs of immunofluorescence analysis of Tnfα positive cells in the experimental groups. Images are representative of staining obtained in sections prepared from at least 5 animals per group. Panels representing DG, CA1 and CA3 region of hippocampus showed TNF-α stained brain tissue at magnification 10× objective field, scale bar= 100 µm. Symbols for treatment groups and level of significance are mentioned in data analysis section of material methods.
Mentions: NFκB activation is the primary event in the progression of the proinflammatory signaling pathway. LPS administration induced iNOS activation and the release of proinflammatory mediators, such as TNF-α and IL-1β, via the NFκB–MAPK pathway27. Font-Nieves et al.3 demonstrated that COX-2 activation followed an NFκB-dependent pathway in LPS-treated samples3. Hippocampal protein expression levels of COX-2, iNOS, TNF-α, and IL-1β were evaluated to examine the effects of LPS and osmotin on the release of inflammatory mediators. Our results demonstrated that LPS treatment for the indicated period induced a higher level of protein expression compared to the vehicle-treated group, and osmotin administration decreased the protein levels of these inflammatory markers in the hippocampus of LPS-injected mice (Fig. 3A). Immunofluorescence detection of TNF-α revealed that osmotin effectively attenuated LPS-induced increases of TNF-α levels in the DG, CA1, and CA3 regions of the hippocampus (Fig. 3B).

Bottom Line: Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1.Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3.Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.

ABSTRACT
Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer's disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.

No MeSH data available.


Related in: MedlinePlus